Use of recombinant antigens to determine the immune status of an animal

ABSTRACT

The present invention includes a method to determine the immune status of an animal that includes the steps of (a) contacting a biological specimen of the animal with a recombinant infectious agent antigen that is specific for detecting an antibody selective for that infectious agent, under conditions suitable for formation of a complex between the recombinant antigen and the antibody and (b) detecting the presence or absence of the complex, wherein presence or absence of a complex is indicative of the immune status of the animal. Preferably such a method indicates whether the animal should be vaccinated. The present invention also includes an assay comprising (a) a recombinant infectious agent antigen that is specific for detecting an antibody selective for that infectious agent; and (b) a means to detect an antibody that selectively binds to the recombinant antigen. Also included in the present invention are recombinant antigens and nucleic acid molecules encoding such antigens as well as methods to produce and use such nucleic acid molecule and recombinant antigens.

FIELD OF THE INVENTION

[0001] The present invention relates generally to materials and methodsuseful for the detection of antibodies in an animal. In particular, theinvention relates to the use of recombinant antigens to determine theimmune status of an animal in order to determine whether the animal hasantibodies indicative of protection from infection by an infectiousagent.

BACKGROUND OF THE INVENTION

[0002] The need for vaccinations against pathogens has long beenrecognized in humans and other animals. The long term efficacy ofvaccines, especially vaccines against viruses, has become a topic ofinterest more recently. One recent study, for example, showed thatneutralizing antibody titers against feline parvovirus (FPV), felineherpesvirus (FHV), and feline calicivirus (FCV) remain in cats for atleast three years following vaccination; see Scott, et al., 1997, FelinePractice 25, 12-19. The antibody titers do decline over time, however,and the exact time that any given cat remains protected against diseasecannot be predicted without testing. Current guidelines for vaccinationrecommend that cats be revaccinated every three years; see, for example,Elston, et al., 1998, Feline Practice 26, 14-16; Elston, et al., 1998,J. Am. Vet. Med. Assoc. 212, 227-241. For dogs, the currentrecommendation is to revaccinate against canine parvovirus and caninedistemper virus yearly.

[0003] Vaccinations, however, are not risk-free. Anaphylaxis,post-vaccine canine distemper encephalitis, polyarthritis,glomerulonephritis, immune-mediated hemolytic anemia, autoimmunenonregenerative anemia and immune-mediated thrombocytopenia are allreported adverse reactions to vaccinations; see, for example, McCaw, etal., 1998, J. Am. Vet. Med. Assoc. 213, 72-75. A small proportion ofcats have also been reported to develop fibrosarcomas after multiplevaccine injections; see, for example, Hershey et al., 2000, J. Am. Vet.Med. Assoc. 216, 58-61. The risks associated with vaccination, coupledwith recent research demonstrating that at least some cats may notrequire certain vaccinations for more than seven years and that at leastsome dogs may not require revaccination for more than two years, areindicative of the desirability of measuring antibody titers to determinethe immune status of animals prior to vaccination; see, Scott, et al.,1999, Am. J. Vet. Res. 60, 652-58 1999; McCaw, et al., ibid.

[0004] The duration of immunity experiments performed by Scott, et al.,1999, ibid., and McCaw, et al., ibid, however, utilized virusneutralization (“VN”) tests to determine the amount of protectiveantibodies in test animals. Depending on the particular assay, VN teststypically require between three and four days to perform, and canrequire as long as six or seven days. Time is only one disadvantage ofthe VN test: the test also requires skilled laboratory personnel toperform, incurs significant cost, and involves the use of live virus,presenting a biohazard risk.

[0005] An enzyme-linked immunosorbent assay (ELISA) represents analternative to VN tests. ELISAs usually require an overnight coatingstep, with the actual test being performed in less than one day. Thistest does require multiple steps and requires a relatively skilledtechnician for performance and analysis. Standard methods use wholevirus or virus-infected cells as the antigen for the detection ofprotective antibodies, again posing a biohazard risk. See, for example,Hill, et al., 1995, Am. J. Vet. Res. 56, 1181-1187; Spencer, et al.,1991, J. Wildl. Dis. 27, 578-583; Fiscus, et al., 1985, Am. J. Vet. Res.46, 859-63. Furthermore, whole virus preparations are contaminated withantigens from the cells used to grow the virus. The procedure forobtaining canine parvovirus (CPV) in Fiscus, et al., ibid., for example,is not sufficient to completely remove such cellular antigens from thepreparation. When using a biological specimen such as blood or serumfrom a vaccinated animal as a test sample, cellular antigens in thevirus preparation can react with antibodies previously produced by theanimal in response to such cellular proteins being in the viruspreparation with which the animal was previously vaccinated. Thepresence of such cellular antigens in an immunoassay frequentlyincreases the level of the signal in the assay, thereby leading to falsepositive or ambiguous results.

[0006] Thus, the methods currently practiced to determine the immunestatus of an animal suffer from a number of disadvantages, which aremultiplied with each antibody type that one wishes to detect.Accordingly, there remains a need for an improved assay for thedetection of antibodies in a test sample that does not require the useof biohazardous material and does not utilize materials containingcontaminants that lead to false positives. There also remains a need foran assay for the detection of antibodies to one or more infectiousagents that can be performed in a relatively short time period, in aveterinarian's office, inexpensively, by unskilled personnel. Therefurther remains a need for antigen reagents that not only are stable andeconomic to produce but also are consistent from batch to batch.

SUMMARY OF THE INVENTION

[0007] The present invention relates generally to materials and methodsuseful for the detection of the immune status of an animal. Inparticular, the invention relates to recombinant antigens and their useas reagents to determine the presence of antibodies indicative ofprotection against disease in an animal.

[0008] One embodiment of the present invention is a method to determinethe immune status of an animal. Such a method includes the steps of: (a)contacting a biological specimen of the animal with a recombinantinfectious agent antigen that is specific for detecting an antibodyselective for that infectious agent, under conditions suitable forformation of a complex between the recombinant antigen and the antibody;and (b) detecting the presence or absence of the complex, whereinpresence or absence of a complex is indicative of the immune status ofthe animal. For example, presence of a complex indicates that the animalis not susceptible to (i.e., is protected from) infection by theinfectious agent.

[0009] Another embodiment of the present invention is a method todetermine whether to vaccinate an animal. Such a method includes thesteps of: (a) contacting a biological specimen of the animal with arecombinant infectious agent antigen that is specific for detecting anantibody selective for that infectious agent, under conditions suitablefor formation of a complex between the recombinant antigen and theantibody; and (b) detecting the presence or absence of the complex.Presence of such a complex indicates that the animal need not bevaccinated, whereas absence of such a complex indicates that the animalshould be vaccinated.

[0010] Yet another embodiment of the present invention is an assay todetermine the immune status of an animal. Such an assay includes (a) arecombinant infectious agent antigen that is specific for detecting anantibody selective for that infectious agent; and (b) a means to detectan antibody that selectively binds to the recombinant antigen.

[0011] The present invention also includes the following recombinantantigens: PFCVCP₆₇₁, PFCVCP₅₄₇, PFPVVP2₅₈₄, PFPVVP2C₂₄₃, PFPVpVP12620,PFPVpVP2₄₇₇, PFHVgB₉₄₃, PFHVgB₂₅₀, PFHVgC₅₃₄, PFHVgC₄₆₇,PFHVgC_(467(opt)), PFHVgD₃₇₄, PFHVgD₃₀₀, PFeLVp27₂₅₃, PFeLVp27₆₁₉,PFeLVp27-gp70₆₁₁, PCDVH₆₀₄, and PCDVF₆₆₂. These recombinant antigens arerepresented, respectively by the following amino acid sequences: SEQ IDNO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12,SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22,SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32,SEQ ID NO:34 and SEQ ID NO:36. Also included are nucleic acid moleculesencoding such recombinant antigens as well as nucleic acid moleculesfully complementary to such coding sequences. Also included arerecombinant molecules and recombinant cells including such nucleic acidmolecules as well as methods to produce such nucleic acid molecules,recombinant molecules, recombinant cells, and recombinant antigens.

DETAILED DESCRIPTION OF THE INVENTION

[0012] The present invention includes a method to determine the immunestatus of an animal. As used herein, the phrase to determine the immunestatus of an animal refers to a method to detect antibodies in thatanimal that are selective for a given infectious agent. Presence of suchantibodies indicates that the animal is protected from infection by theinfectious agent. Such an animal need not be vaccinated as it is notsusceptible to infection by the infectious agent. A method of thepresent invention to determine the immune status of an animal includesthe steps of: (a) contacting a biological specimen of the animal with arecombinant infectious agent antigen that is specific for detecting anantibody selective for that infectious agent, under conditions suitablefor formation of a complex between the recombinant antigen and theantibody; and (b) detecting the presence or absence of the complex,wherein presence or absence of a complex is indicative of the immunestatus of the animal. In one embodiment, such a method is used todetermine whether to vaccinate an animal. The present invention alsoincludes an assay to determine the immune status of an animal as well asrecombinant antigens that can be used in such a method or assay. Alsoincluded are nucleic acid molecules encoding such recombinant antigens,recombinant molecules and recombinant cells as well as methods toproduce and use such molecules and cells.

[0013] It was surprising to the inventors that recombinant antigens areessential to a method to accurately determine the immune status of ananimal. Use of whole virus in such a method was found to be unacceptabledue to the potential for false positives caused by cellular antigensco-purifying with the virus preparation. The problem with cellularantigens was compounded when virus was isolated in a large-scalepreparation. Although attempts were made to overcome these problems,using, for example, ultracentrifugation or cesium chloride purificationtechniques to purify virus, unacceptable levels of cellular antigensremained. As described in more detail in the Examples, not only didreagents containing feline calicivirus (FCV), feline herpesvirus (FHV),or feline parvovirus (FPV) purified from Crandell feline kidney (CRFK)cells in which the respective virus had grown (i.e., FCV or FHV purifiedby ultracentrifugation or FPV through cesium chloride) yield positiveresults in an ELISA to detect antibodies in cats previously administeredthe respective virus, but so did the respective “control” reagentspurified from uninfected CRFK cells in the same manner. Data obtainedfrom the “control” reagents represented unacceptable false positiveresults, leading the inventors to pursue alternative routes to developan immune status assay. The inventors subsequently found that arecombinantly produced viral antigen yields unexpectedly good results,with acceptable background levels, in the determination of the immunestatus of an animal by immunoassay.

[0014] As such, the present invention includes a method to determine theimmune status of an animal that includes the following steps: (a)contacting a biological specimen of the animal with a recombinantinfectious agent antigen that is specific for detecting an antibodyselective for that infectious agent, under conditions suitable forformation of a complex between the recombinant antigen and the antibody;and (b) detecting the presence or absence of the complex, whereinpresence or absence of a complex is indicative of the immune status ofthe animal. It is to be noted that the term “a” entity or “an” entityrefers to one or more of that entity; for example, a recombinant antigenrefers to one or more antigens or at least one antigen. As such, theterms “a” (or “an”), “one or more” and “at least one” can be usedinterchangeably herein. It is also to be noted that the terms“comprising”, “including”, and “having” can be used interchangeably.

[0015] As used herein, a recombinant infectious agent antigen is anantigen of an infectious agent that is produced using recombinantnucleic acid technology. Such an antigen, also referred to herein as arecombinant antigen of the present invention or simply as a recombinantantigen, can be identified in a straight-forward manner by its abilityto specifically detect an antibody selective for that infectious agent.As used herein, an antibody selective for an infectious agent, alsoreferred to herein as an anti-infectious agent antibody, is an antibodythat selectively binds to that infectious agent in that itpreferentially binds to that infectious agent as opposed to binding to adifferent, unrelated, infectious agent. It is to be noted that, inaccordance with the present invention, such an antibody exists in abiological specimen of an animal because a given infectious agent, uponinfecting the animal, induces an immune response that includes theproduction of such an antibody selective for that infectious agent. Arecombinant antigen of the present invention is also able tospecifically detect the presence of such an antibody in that therecombinant antigen is sufficiently similar to the corresponding antigenon the infectious agent to enable such detection. The specificity ofsuch detection enables one to ascertain that an animal has antibodies toa given infectious agent rather than to an unrelated infectious agent.Binding of an antigen and antibody can be measured using a variety ofmethods known to those skilled in the art, such as, but not limited to,those methods disclosed elsewhere herein. Preferably, a recombinantantigen of the present invention has a binding affinity of from about10⁸ liters per mole (M⁻¹) to about 10¹² M⁻¹ for an anti-infectious agentantibody of the present invention.

[0016] A recombinant infectious agent antigen of the present inventioncan correspond exactly to the antigen as found on the infectious agentor the recombinant antigen can be a homolog of such a native antigen.Examples of homologs include proteins in which amino acids have beendeleted (e.g., a truncated version of the protein, such as a peptide),inserted, inverted, substituted and/or derivatized (e.g., byglycosylation, phosphorylation, acetylation, myristoylation,prenylation, palmitoylation, amidation and/or addition ofglycerophosphatidyl inositol) such that the homolog includes at leastone epitope capable of forming an immunocomplex, also referred to hereinas a complex, with an anti-infectious agent antibody. As used herein,the term epitope refers to the smallest portion of a protein or otherantigen capable of selectively binding to the antigen binding site of anantibody. It is well accepted by those skilled in the art that theminimal size of a protein epitope is about four amino acids. In oneembodiment, a recombinant antigen of the present invention is modifiedto produce a more soluble antigen. Methods to produce more solubleantigens by modifying either a nucleic acid sequence or the proteinitself are well known to those skilled in the art. One example of such amethod, not intended to be limiting, is protein iodoacetimidation.

[0017] A recombinant antigen homolog can be the result of naturalallelic variation or natural mutation. Homologs of the present inventioncan also be produced using techniques known in the art including, butnot limited to, direct modifications to the protein or modifications tothe nucleic acid molecule encoding the protein using, for example,classic or recombinant nucleic acid molecule techniques to effect randomor targeted mutagenesis.

[0018] It is to be appreciated that recombinant antigens of the presentinvention include, but are not limited to, full-length proteins,proteins that are encoded by allelic variants of a given nucleic acidsequence, hybrid proteins, fusion proteins, multivalent proteins, andproteins that are truncated homologs of, or are proteolytic products of,at least a portion of a protein. As used herein, the term hybrid proteinrefers to a single protein produced from at least two differentproteins; i.e., having domains from at least two different proteins.

[0019] Due to the method by which it is produced, a recombinant antigenof the present invention is removed from its natural milieu. As such, arecombinant antigen is isolated or biologically pure. Such terms do notreflect the extent to which a recombinant antigen is purified. Apreferred recombinant antigen is purified from the recombinant cellwhich expresses the protein. Examples of methods to produce recombinantantigens of the present invention are disclosed elsewhere herein.

[0020] A recombinant infectious agent antigen of the present inventionis any recombinant antigen that corresponds to (e.g., is derived from)an infectious agent. Preferred is an infectious agent for which onedesires to determine if an animal is susceptible to infection by thatagent. Suitable infectious agents include, but are not limited to,viruses, bacteria, fungi, endoparasites and ectoparasites. As such,suitable recombinant infectious agent antigens include, but are notlimited to, recombinant viral, bacterial, fungal, endoparasite andectoparasite antigens. Examples of viral infectious agents include, butare not limited to, adenoviruses, caliciviruses, coronaviruses,distemper viruses, hepatitis viruses, herpesviruses, immunodeficiencyviruses, infectious peritonitis viruses, leukemia viruses, oncogenicviruses, papilloma viruses, parainfluenza viruses, parvoviruses, rabiesviruses, and reoviruses, as well as other cancer-causing orcancer-related viruses. Examples of bacterial infectious agents include,but are not limited to, Actinomyces, Bacillus, Bacteroides, Bartonella,Bordetella, Borrelia, Brucella, Campylobacter, Capnocytophaga,Clostridium, Corynebacterium, Coxiella, Dermatophilus, Ehrlichia,Enterococcus, Escherichia, Francisella, Fusobacterium, Haemobartonella,Helicobacter, Klebsiella, L-form bacteria, Leptospira, Listeria,Mycobacteria, Mycoplasma, Neorickettsia, Nocardia, Pasteurella,Peptococcus, Peptostreptococcus, Proteus, Pseudomonas, Rickettsia,Rochalimaea, Salmonella, Shigella, Staphylococcus, Streptococcus, andYersinia. Examples of fungal infectious agents include, but are notlimited to, Absidia, Acremonium, Altemaria, Aspergillus, Basidiobolus,Bipolaris, Blastomyces, Candida, Chlamydia, Coccidioides, Conidiobolus,Cryptococcus, Curvalaria, Epidermophyton, Exophiala, Geotrichum,Histoplasma, Madurella, Malassezia, Microsporum, Moniliella,Mortierella, Mucor, Paecilomyces, Penicillium, Phialemonium,Phialophora, Pro to theca, Pseudallescheria, Pseudomicrodochium,Pythium, Rhinosporidium, Rhizopus, Scolecobasidium, Sporothrix,Stemphylium, Trichophyton, Trichosporon, and Xylohypha. Example ofprotozoan parasite infectious agents include, but are not limited to,Babesia, Balantidium, Besnoitia, Cryptosporidium, Eimeria,Encephalitozoon, Entamoeba, Giardia, Hammondia, Hepatozoon, Isospora,Leishmania, Microsporidia, Neospora, Nosema, Pentatrichomonas,Plasmodium, Pneumocystis, Sarcocystis, Schistosoma, Theileria,Toxoplasma, and Trypanosoma. Examples of helminth parasite infectiousagents include, but are not limited to, Acanthocheilonema,Aelurostrongylus, Ancylostoma, Angiostrongylus, Ascaris, Brugia,Bunostomum, Capillaria, Chabertia, Cooperia, Crenosoma, Dictyocaulus,Dioctophyme, Dipetalonema, Diphyllobothrium, Diplydium, Dirofilaria,Dracunculus, Enterobius, Filaroides, Haemonchus, Lagochilascaris, Loa,Mansonella, Muellerius, Nanophyetus, Necator, Nematodirus,Oesophagostomum, Onchocerca, Opisthorchis, Ostertagia, Parafilaria,Paragonimus, Parascaris, Physaloptera, Protostrongylus, Setaria,Spirocerca, Spirometra, Stephanofilaria, Strongyloides, Strongylus,Thelazia, Toxascaris, Toxocara, Trichinella, Trichostrongylus,Trichuris. Uncinaria, and Wuchereria. Examples of ectoparasiteinfectious agents include, but are not limited to, fleas; ticks,including hard ticks and soft ticks; flies, such as midges, mosquitos,sand flies, black flies, horse flies, horn flies, deer flies, tsetseflies, stable flies, myiasis-causing flies and biting gnats; ants;spiders, lice; mites; and true bugs, such as bed bugs and kissing bugs.

[0021] Preferred recombinant antigens of the present invention includean adenovirus protein, a calicivirus protein, a coronavirus protein, adistemper virus protein, a herpesvirus protein, an immunodeficiencyvirus protein, an influenza virus protein, a leukemia virus protein, aparvovirus protein, a rabies virus protein, a Bartonella protein, anEhrlichia protein, a Haemobartonella protein, a Leptospira protein, aStreptococcus protein, a protozoan myeloecephalitis protein, aDirofilaria protein, and a Giardia protein. More preferred recombinantantigens include a feline calicivirus protein, a feline coronavirusprotein, a feline herpesvirus protein, a feline leukemia virus protein,a feline parvovirus protein, a canine adenovirus protein, a caninecoronavirus protein, a canine distemper virus protein, a canineparvovirus protein, a rabies virus protein, an equine herpesvirus Iprotein, an equine herpesvirus IV protein, an equine influenza virusprotein, a Streptococcus equii protein, and an Ehrlichia protein. Evenmore preferred recombinant antigens of the present invention include afeline calicivirus capsid protein (a rFCVCP protein), a felineherpesvirus glycoprotein B (gB) protein (a rFHVgB protein), a felineherpesvirus glycoprotein C (gC) protein (a rFHVgC protein), a felineherpesvirus glycoprotein D (gD) protein (a rFHV gD protein), a felineparvovirus VP12 protein (a rFPVVP12 protein), a feline parvovirus VP2protein (a rFPVVP2 protein), a feline leukemia virus p27 protein (arFeLVp27 protein), a feline leukemia virus glycoprotein70 protein (arFeLVgp70 protein), a p27/gp70 fusion protein (a rFeLVp27-gp70 protein),a canine distemper virus fusion protein (a rCDVF protein), and a caninedistemper virus hemagglutinin protein (a rCDVH protein). Even morepreferred recombinant antigens of the present invention includePFCVCP₆₇, PFCVCP₅₄₇, PFPVVP2₅₈₄, PFPVVP2C₂₄₃, PFPVpVP12620, PFPVpVP2₄₇₇,PFHVgB₉₄₃, PFHVgB₂₅₀, PFHVgC₅₃₄, PFHVgC₄₆₇, PFHVgC_(467(opt)),PFHVgD₃₇₄, PFHVgD₃₀₀, PFeLVp27₂₅₃, PFeLVp27₆₁₉, PFeLVp27-gp70₆₁₁,PCDVH₆₀₄, and PCDVF₆₆₂, the characteristics and production of which aredescribed in the Examples. Such recombinant proteins have the followingrespective amino acid sequences: SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6,SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ IDNO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34 and SEQ ID NO:36.

[0022] Particularly preferred recombinant antigens of the presentinvention include proteins having at least one of the following aminoacid sequences: SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ IDNO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ IDNO:30, SEQ ID NO:32, SEQ ID NO:34 and SEQ ID NO:36. Also preferred arerecombinant antigens that are fragments of any of such antigens havingsuch cited amino acid sequences, the fragments being able to bind toantibodies selective for the corresponding infectious agent. Preferredrecombinant antigens can be encoded by nucleic acid molecules that: (a)have at least one of the following nucleic acid sequences: SEQ ID NO:1,SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ IDNO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ IDNO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ IDNO:33, and SEQ ID NO:35; (b) are degenerates of the nucleic acidsequences of (a); (c) are allelic variants of the nucleic acid sequencesof (a); or (d) are fragments of any of the nucleic acid molecules of(a), (b), or (c). The foregoing SEQ ID NOs represent nucleic acid andamino acid sequences deduced according to methods disclosed in theExamples. It should be noted that since nucleic acid sequencingtechnology is not entirely error-free, the foregoing SEQ ID NOs, atbest, represent apparent nucleic acid and amino acid sequences ofcertain nucleic acid molecules and recombinant antigens, respectively,of the present invention. In addition, variation seen in the foregoingSEQ ID NOs can also be due, at least in part, to allelic variation,which can be caused by, among other factors, genetic drift.

[0023] Additional preferred recombinant antigens of the presentinvention share at least about 70%, preferably at least about 75%, morepreferably at least about 80%, more preferably at least about 85%, morepreferably at least about 90%, more preferably at least about 95%, andmore preferably about 100% identity at the amino acid level with aprotein having at least one of the following amino acid sequences: SEQID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ IDNO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ IDNO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ IDNO:32, SEQ ID NO:34 and SEQ ID NO:36. Also preferred are fragments ofsuch antigens, and particularly fragments that are at least about 5, 10,15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350,400, 450, 500, 550, 600, 650, 700, 750, 800, 850, or 900 amino acids inlength.

[0024] The present invention also includes a recombinant antigen nucleicacid molecule. Recombinant antigen nucleic acid molecules of the presentinvention include any recombinant nucleic acid molecule that encodes arecombinant antigen of the present invention as well as a nucleic acidmolecule fully complementary to any such coding sequence. A nucleic acidmolecule of the present invention can be single-stranded ordouble-stranded. In accordance with the present invention, an isolatednucleic acid molecule is a nucleic acid molecule that has been removedfrom its natural milieu, i.e., that has been subjected to humanmanipulation, and can include DNA, RNA, or derivatives of either DNA orRNA. It is to be noted that the term isolated does not reflect theextent to which the nucleic acid molecule has been purified. Arecombinant antigen nucleic acid molecule of the present invention canbe isolated from its natural source or produced using recombinant DNAtechnology, e.g., polymerase chain reaction (PCR) amplification orcloning, or chemical synthesis. Although the phrase, nucleic acidmolecule, primarily refers to the physical nucleic acid molecule and thephrase, nucleic acid sequence, primarily refers to the sequence ofnucleotides on the nucleic acid molecule, the two phrases can be usedinterchangeably.

[0025] A nucleic acid molecule of the present invention can be a naturalisolate or a homolog thereof. Nucleic acid molecule homologs includenatural allelic variants and nucleic acid molecules modified by one ormore nucleotide insertions, deletions, substitutions, and/or inversionsin a manner such that the modification(s) do not substantially interferewith the nucleic acid molecule's ability to encode a recombinant antigenof the present invention. A nucleic acid molecule homolog of the presentinvention can be produced using a number of methods known to thoseskilled in the art; see, for example, Sambrook et al., 1989, MolecularCloning: A Laboratory Manual, Cold Spring Harbor Labs Press; Sambrook etal., ibid., is incorporated by reference herein in its entirety. Forexample, nucleic acid molecules can be modified using a variety oftechniques including, but not limited to, classic mutagenesis andrecombinant DNA techniques such as site-directed mutagenesis, chemicaltreatment, restriction enzyme cleavage, ligation of nucleic acidfragments, PCR amplification, synthesis of oligonucleotide mixtures andligation of mixture groups to build a mixture of nucleic acid molecules,and combinations thereof. Nucleic acid molecule homologs can be selectedby hybridization or by screening for the function of a protein encodedby the nucleic acid molecule, e.g., ability to detect antibodiesselective for the corresponding infectious agent.

[0026] Suitable and preferred nucleic acid molecules of the presentinvention encode suitable and preferred recombinant antigens asdisclosed herein. Particularly preferred nucleic acid molecules of thepresent invention include the following nucleic acid sequences: SEQ IDNO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11,SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21,SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31,SEQ ID NO:33, and SEQ ID NO:35; as well as nucleic acid molecules havingnucleic acid sequences fully complementary to such sequences.Particularly preferred double-stranded nucleic acid molecules includenFCVCP₂₀₁₃, nFCVCP₁₆₄₁, nFPVVP2₁₇₅₂, nFPVVP2C₇₂₉, nFPVpVP12₁₈₆₀,nFPVpVP2₁₄₃₁, nFHVgB₂₈₂₉, nFHVgB₇₅₀, nFHVgC₁₆₀₂, nFHVgC₁₄₀₁,nFHVgC_(1401(opt)), nFHVgD₁₁₂₂, nFHVgD₉₀₀, nFeLVp27₇₅₉, nFeLVp27₁₈₅₇,nFeLVp27-gp70₁₈₃₃, nCDVH₁₈₁₂, and nCDVF₁₉₈₆. Also preferred are nucleicacid molecules having degenerate sequences to any of the afore-mentionednucleic acid molecules having cited nucleic acid sequences and nucleicacid molecules that are allelic variants thereof as well as fragments ofany of the above-mentioned nucleic acid molecules. As used herein anucleic acid molecule having a sequence that is degenerate as comparedto a cited nucleic acid sequence is a nucleic acid molecule that encodesthe same protein as the nucleic acid molecule having the cited sequence,but has a different nucleic acid sequence due to the degeneracy of thegenetic code. As used herein, an allelic variant of a nucleic acidmolecule having a cited nucleic acid sequence is a nucleic acid moleculethat is a gene occurring at essentially the same locus (or loci) in thegenome as the gene including the particular SEQ ID NO's cited herein,but which, due to natural variations caused by, for example, mutation orrecombination, has a similar but not identical sequence. Also includedin the term allelic variant are allelic variants of cDNAs derived fromsuch genes. Because natural selection typically selects againstalterations that affect function, allelic variants usually encodeproteins having similar activity to that of the protein encoded by thegene to which they are being compared. Allelic variants of nucleic acidmolecules can also comprise alterations in the 5′ or 3′ untranslatedregions of the gene (e.g., in regulatory control regions), or caninvolve alternative splicing of a nascent transcript, thereby bringingalternative exons into juxtaposition. Allelic variants are well known tothose skilled in the art and would be expected to be found within agiven infectious agent.

[0027] Additional preferred recombinant antigen nucleic acid moleculesof the present invention share at least about 70%, preferably at leastabout 75%, more preferably at least about 80%, more preferably at leastabout 85%, more preferably at least about 90%, more preferably at leastabout 95%, and more preferably about 100% identity at the nucleic acidlevel with a nucleic acid molecule having at least one of the followingnucleic acid sequences: SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ IDNO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ IDNO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ IDNO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, and SEQ ID NO:35. Alsopreferred are fragments of such nucleic acid molecules, an particularlyfragments that are at least about 15, 20, 25, 30, 40, 50, 60, 70, 80,90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700,750, 800, 850, 900, 950, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700,1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, or 2800nucleotides in length.

[0028] The minimal size of a recombinant antigen of the presentinvention is a size sufficient to be encoded by a nucleic acid moleculecapable of forming a stable hybrid (i.e., hybridize under stringenthybridization conditions) with the complementary sequence of a nucleicacid molecule encoding the corresponding protein. The size of a nucleicacid molecule encoding such a protein is dependent on the nucleic acidcomposition and the percent homology between the nucleic acid moleculeand the complementary nucleic acid sequence. It can easily be understoodthat the extent of homology required to form a stable hybrid understringent conditions can vary depending on whether the homologoussequences are interspersed throughout a given nucleic acid molecule orare clustered (i.e., localized) in distinct regions on a given nucleicacid molecule.

[0029] The minimal size of a nucleic acid molecule capable of forming astable hybrid with a nucleic acid molecule encoding a recombinantantigen is typically at least about 12 to about 15 nucleotides in lengthif the nucleic acid molecule is GC-rich and at least about 15 to about17 nucleotides in length if it is AT-rich. The minimal size of a nucleicacid molecule used to encode a recombinant antigen homolog of thepresent invention is from about 12 to about 18 nucleotides in length.Thus, the minimal size of a recombinant antigen homolog of the presentinvention is from about 4 to about 6 amino acids in length. There is nolimit, other than a practical limit, on the maximal size of a nucleicacid molecule encoding a recombinant antigen of the present inventionbecause a nucleic acid molecule of the present invention can include aportion of a full-length coding region, a full-length coding region, ormultiple coding regions (either partial or full-length). The preferredsize of a protein encoded by a nucleic acid molecule of the presentinvention depends on whether a full-length, fusion, multivalent, orfunctional portion of such a protein is desired.

[0030] Stringent hybridization conditions are determined based ondefined physical properties of the target nucleic acid molecule to whicha nucleic acid molecule is being hybridized, and can be definedmathematically. Stringent hybridization conditions are thoseexperimental parameters that allow an individual skilled in the art toidentify significant similarities between heterologous nucleic acidmolecules, i.e., those conditions that allow the identification ofnucleic acid molecules that are at least about 70% identical, or thatshare less than about 30% mismatch. These conditions are well known tothose skilled in the art. See, for example, Sambrook, et al., 1989,ibid., and Meinkoth, et al., 1984, Anal. Biochem. 138, 267-284;Meinkoth, et al., is incorporated by reference herein in its entirety.

[0031] Furthermore, it is known in the art that there are commerciallyavailable computer programs for determining the degree of similaritybetween two nucleic acid sequences or amino acid sequences. Thesecomputer programs include various known methods to determine thepercentage identity and the number and length of gaps between nucleicacid molecules and proteins. It is further known that the variousavailable sequence analysis programs produce substantially similarresults when the two compared molecules encode amino acid sequences thathave greater than 30% amino acid identity. See Johnson et al., 1993 J.Mol. Biol. 233, 716-738, 1993, and Feng et al., 1985, J. Mol. Evol. 21,112-125, 1985, each of which is incorporated by reference herein in itsentirety. Preferred methods to determine the percent identity amongamino acid sequences and also among nucleic acid sequences includeanalysis using one or more of the commercially available computerprograms designed to compare and analyze nucleic acid or amino acidsequences. These computer programs include, but are in no way limitedto, GCG™ (available from Genetics Computer Group, Madison, Wis.),DNAsis™ (available from Hitachi Software, San Bruno, Calif.) andMacVector™ (available from the Eastman Kodak Company, New Haven, Conn.).A particularly preferred method to determine the percent identity amongamino acid sequences and also among nucleic acid sequences is to performthe analysis using the DNAsis™ computer program, using defaultparameters.

[0032] The present invention also includes mimetopes of recombinantantigens of the present invention. In accordance with the presentinvention, a “mimetope” refers to any compound that is able to mimic theability of a recombinant antigen of the present invention to bind to anantibody. A mimetope can be a peptide that has been modified to decreaseits susceptibility to degradation but that still retainsantibody-binding activity. Other examples of mimetopes include, but arenot limited to, carbohydrate-based compounds, lipid-based compounds,nucleic acid-based compounds, natural organic compounds, syntheticallyderived organic compounds, anti-idiotypic antibodies and/or catalyticantibodies, or fragments thereof. A mimetope can be obtained by, forexample, screening libraries of synthetic compounds for compoundscapable of binding to anti-infectious agent antibodies. A mimetope canalso be obtained by, for example, rational drug design. In a rationaldrug design procedure, the three-dimensional structure of a compound ofthe present invention can be analyzed by, for example, nuclear magneticresonance (NMR) or x-ray crystallography. The three-dimensionalstructure can then be used to predict structures of potential mimetopesby, for example, computer modeling. The predicted mimetope structurescan then be produced by, for example, chemical synthesis, recombinantDNA technology, or by isolation from a natural source.

[0033] One embodiment of the present invention includes a recombinantvector that includes at least one isolated nucleic acid molecule of thepresent invention, inserted into any vector capable of delivering thenucleic acid molecule into a host cell. Such a vector containsheterologous nucleic acid sequences, that is nucleic acid sequences thatare not naturally found adjacent to nucleic acid molecules of thepresent invention and that preferably are derived from a species otherthan the species from which the nucleic acid molecule(s) are derived.The vector can be either RNA or DNA, either prokaryotic or eukaryotic,and typically is a virus or a plasmid. Recombinant vectors can be usedin the cloning, sequencing, and/or otherwise manipulating of antigennucleic acid molecules of the present invention.

[0034] One type of recombinant vector, referred to herein as arecombinant molecule, comprises a nucleic acid molecule of the presentinvention operatively linked to an expression vector. The phraseoperatively linked refers to insertion of a nucleic acid molecule intoan expression vector in a manner such that the molecule is able to beexpressed when transformed into a host cell. As used herein, anexpression vector is a DNA or RNA vector that is capable of transforminga host cell and of effecting expression of a specified nucleic acidmolecule. Preferably, the expression vector is also capable ofreplicating within the host cell. Expression vectors can be eitherprokaryotic or eukaryotic, and are typically viruses or plasmids.Expression vectors of the present invention include any vectors thatfunction (i.e., direct gene expression) in recombinant cells of thepresent invention, including in bacterial, fungal, parasite, insect,other animal, and plant cells. Preferred expression vectors of thepresent invention can direct gene expression in bacterial, yeast, insectand mammalian cells, and more preferably in bacteria.

[0035] In particular, expression vectors of the present inventioncontain regulatory sequences such as transcription control sequences,translation control sequences, origins of replication, and otherregulatory sequences that are compatible with the recombinant cell andthat control the expression of nucleic acid molecules of the presentinvention. In particular, recombinant molecules of the present inventioninclude transcription control sequences. Transcription control sequencesare sequences which control the initiation, elongation, and terminationof transcription. Particularly important transcription control sequencesare those which control transcription initiation, such as promoter,enhancer, operator and repressor sequences. Suitable transcriptioncontrol sequences include any transcription control sequence that canfunction in at least one of the recombinant cells of the presentinvention. A variety of such transcription control sequences are knownto those skilled in the art. Preferred transcription control sequencesinclude those which function in bacterial, yeast, insect or mammaliancells. More preferred transcription control sequences include those thatfunction in bacteria, such as, but not limited to, tac, lac, trp, trc,oxy-pro, omp/lpp, rrnB, bacteriophage lambda (such as lambda PL andlambda PR and fusions that include such promoters), bacteriophage T7,T71ac, bacteriophage T3, bacteriophage SP6, bacteriophage SP01, andantibiotic resistance gene transcription control sequences.

[0036] Suitable and preferred nucleic acid molecules to include inrecombinant vectors of the present invention are as disclosed herein.Preferred nucleic acid molecules to include in recombinant vectors, andparticularly in recombinant molecules, include nFCVCP₂₀₁₃, nFCVCP₁₆₄₁,nFPVVP2₁₇₅₂, nFPVVP2C₇₂₉, nFPVpVP12₆₁₈₆₀, nFPVpVP2₁₄₃₁, nFHVgB₂₈₂₉,nFHVgB₇₅₀, nFHVgC₁₆₀₂, nFHVgC₁₄₀₁, nFHVgC_(1401(opt)), nFHVgD₁₁₂₂,nFHVgD₉₀₀, nFeLVp27₇₅₉, nFeLVp27₁₈₅₇, nFeLVp27-gp70₁₈₃₃, nCDVH₈₁₂, andnCDVF₁₉₈₆. Particularly preferred recombinant molecules of the presentinvention include pλP_(R)His-nFCVCP₂₀₁₃, pλP_(R)-nFCVCP₁₆₄₁,pλP_(R)His-nFPVVP2₁₇₅₂, pλP_(R)His-nFPVVP2C₇₂₉, pλP_(R)-nFPVVP2C₇₂₉,pλP_(R)His-nFPVpVP12₁₈₆₀, pλP_(R)His-nFPVpVP2₁₄₃₁, pλP_(R)-nFPVpVP2₁₄₃₁,pλP_(R)His-nFHVgB₂₈₂₉, pλP_(R)His-nFHVgB₇₅₀, pλP_(R)His-nFHVgC₁₆₀₂,pλP_(R)His-nFHVgC₁₄₀₁, pλP_(R)-nFHVgC_(1401(opt)),pλP_(R)His-nFHVgD₁₁₂₂, pλP_(R)His-nFHVgD₉₀₀, pλP_(R)-nFeLVp27₇₅₉,pλP_(R)His-nFeLVp27₁₈₅₇, pλP_(R)-nFeLVp27-gp70₁₈₃₃,pλP_(R)His-nCDVH₁₈₁₂, and pλP_(R)His-nCDVF₁₉₈₆, the production of whichare described in the Examples section.

[0037] Recombinant molecules of the present invention may also (a)contain secretory signals (i.e., signal segment nucleic acid sequences)to enable an expressed antigen of the present invention to be secretedfrom the cell that produces the protein and/or (b) contain fusionsequences which lead to the expression of nucleic acid molecules of thepresent invention as fusion proteins. Examples of suitable signalsegments include any signal segment capable of directing the secretionof a protein of the present invention. Suitable fusion segments for usewith the present invention include, but are not limited to, segmentsthat can: enhance a protein's stability, enhance attachment of a proteinto a substrate, and/or assist purification of a isolated antigen of thepresent invention (e.g., by affinity chromatography). A suitable fusionsegment can be a domain of any size that has the desired function (e.g.,imparts increased stability, enhances attachment to a substrate, and/orsimplifies purification of a protein). Fusion segments can be joined toamino and/or carboxyl termini of the of the protein and can besusceptible to cleavage in order to enable straight-forward recovery ofa isolated antigen of the present invention. Fusion proteins arepreferably produced by culturing a recombinant cell transformed with afusion nucleic acid molecule that encodes a protein including the fusionsegment attached to either the carboxyl and/or amino terminal end of adomain. Preferred fusion segments include a metal binding domain (e.g.,a poly-histidine segment); an immunoglobulin binding domain (e.g.,Protein A; Protein G; T cell; B cell; Fc receptor or complement proteinantibody-binding domains); a sugar binding domain (e.g., a maltosebinding domain); and/or a “tag” domain (e.g., at least a portion ofO-galactosidase, a strep tag peptide, other domains that can be purifiedusing compounds that bind to the domain, such as monoclonal antibodies).A more preferred fusion segment is a metal binding domain. Examples ofparticularly preferred fusion proteins of the present invention includePHis-PFCVCP₆₇₁, PHis-PFCVCP₅₄₇, PHis-PFPVVP2₅₈₄, PHis-PFPVVP2C₂₄₃,PHis-PFPVpVP12620, PHis-PFPVpVP2₄₇₇, PHis-PFHVgB₉₄₃, PHis-PFHVgB₂₅₀,PHis-PFHVgC₃₄, PHis-PFHVgC₄₆₇, PHis-PFHVgC_(467(opt)), PHis-PFHVgD₃₇₄,PHis-PFHVgD₃₀₀, PHis-PFeLVp27₂₅₃, PHis-PFeLVp27₆₁₉,PHis-PFeLVp27-gp70₆₁₁, PHis-PCDVH₆₀₄, and PHis-PCDVF₆₆₂; methods toproduce such fusion proteins are disclosed in the Examples. The presentinvention also includes post-translational modification of a recombinantantigen to introduce a ligand. Examples of ligands include biotin,biotin-like compounds, avidin, avidin-like compounds, metal bindingcompounds, sugar binding compounds, immunoglobulin binding domains, andother tag domains.

[0038] Another embodiment of the present invention includes arecombinant cell comprising a host cell transformed with one or morenucleic acid molecules or recombinant molecules of the presentinvention. Transformation of a nucleic acid molecule into a cell can beaccomplished by any method by which a nucleic acid molecule can beinserted into the cell. Transformation techniques include, but are notlimited to, transfection, electroporation, microinjection, lipofection,adsorption, and protoplast fusion. Transformed nucleic acid molecules ofthe present invention can remain extrachromosomal or can integrate intoone or more sites within a chromosome of the transformed (i.e.,recombinant) cell in such a manner that their ability to be expressed isretained. Suitable nucleic acid molecules with which to transform a cellinclude any nucleic acid molecules disclosed herein that encode arecombinant antigen. Particularly preferred nucleic acid molecules withwhich to transform a cell include nFCVCP₂₀₁₃, nFCVCP₁₆₄₁, nFPVVP2₁₇₅₂,nFPVVP2C₇₂₉, nFPVpVP12₁₈₆₀, nFPVpVP2₁₄₃₁, nFHVgB₂₈₂₉, nFHVgB₇₅₀,nFHVgC₁₆₀₂, nFHVgC₁₄₀₁, nFHVgC_(1401(opt)), nFHVgD₁₁₂₂, nFHVgD₉₀₀,nFeLVp27₇₅₉, nFeLVp27₈₅₇, nFeLVp27-gp70₁₈₃₃, nCDVH₁₈₁₂, and nCDVF₁₉₈₆.

[0039] Suitable host cells to transform include any cell that can betransformed with a nucleic acid molecule of the present invention. Hostcells can be either untransformed cells or cells that are alreadytransformed with at least one nucleic acid molecule. Host cells of thepresent invention can be any cell capable of producing at least oneprotein of the present invention, and include bacterial, fungal(including yeast), parasite (including helminth, protozoa andectoparasite), other insect, other animal and plant cells. Preferredhost cells include bacterial, mycobacterial, yeast, insect and mammaliancells. More preferred host cells include Salmonella, Escherichia,Bacillus, Listeria, Saccharomyces, Pichia, Spodoptera, Mycobacteria, andTrichoplusia cells. Particularly preferred host cells are Escherichiacoli.

[0040] A recombinant cell is preferably produced by transforming a hostcell with a recombinant molecule encoding a recombinant antigen of thepresent invention operatively linked to an expression vector containinga transcription control sequence. Particularly preferred recombinantmolecules include pλP_(R)His-nFCVCP₂₀₁₃, pλP_(R)-nFCVCP₁₆₄₁,pλP_(R)His-nFPVVP2₁₇₅₂, pλP_(R)His-nFPVVP2C₇₂₉, pλP_(R)-nFPVVP²C₇₂₉,pλP_(R)His-nFPVpVP12₁₈₆₀, pλP_(R)His-nFPVpVP2₁₄₃₁, pλP_(R)-nFPVpVP2₁₄₃₁,pλP_(R)His-nFHVgB₂₈₂₉, pλP_(R)His-nFHVgB₇₅₀, pλP_(R)His-nFHVgC₁₆₀₂,pλP_(R)His-nFHVgC₁₄₀₁, pλP_(R)-nFHVgC_(1401(opt)),pλP_(R)His-nFHVgD₁₁₂₂, pλP_(R)His-nFHVgD₉₀₀, pλP_(R)-nFeLVp27₇₅₉,pλP_(R)His-nFeLVp27₁₈₅₇, pλP_(R)-nFeLVp27-gp70₁₈₃₃,pλP_(R)His-nCDVH₁₈₁₂, and pλP_(R)His-nCDVF₁₉₈₆. Particularly preferredrecombinant cells include E. coli:pλP_(R)His-nFCVCP₂₀₁₃ , E.coli:pλP_(R)-nFCVCP₁₆₄₁ , E. coli:pλP_(R)His-nFPVVP21₇₅₂ , E.coli:pλP_(R)His-nFPVVP2C₇₂₉ , E. coli:pλP_(R)-nFPVVP2C₇₂₉ , E.coli:pλP_(R)His-nFPVpVP121860, E. coli:pλP_(R)His-nFPVpVP2₁₄₃₁ , E.coli:pλP_(R)-nFPVpVP2₁₄₃₁ , E. coli:pλP_(R)His-nFHVgB₂₈₂₉ , E.coli:pλP_(R)His-nFHVgB₇₅₀ , E. coli:pλP_(R)His-nFHVgC₁₆₀₂ , E.coli:pλP_(R)His-nFHVgC₁₄₀₁ , E. coli:pλP_(R)-nFHVgC_(1401(opt)) , E.coli:pλP_(R)His-nFHVgD₁₁₂₂ , E. coli:pλP_(R)His-nFHVgD₉₀₀ , E.coli:pλP_(R)-nFeLVp27₇₅₉ , E. coli:pλP_(R)His-nFeLVp27₁₈₅₇ , E.coli:pλP_(R)-nFeLVp27-gp70₁₈₃₃ , E. coli:pλP_(R)His-nCDVH₁₈₁₂, and E.coli:pλP_(R)His-nCDVF₁₉₈₆. Details regarding the production of theserecombinant cells are disclosed herein.

[0041] Recombinant DNA technologies can be used to improve expression oftransformed nucleic acid molecules by manipulating, for example, thenumber of copies of the nucleic acid molecules within a host cell, theefficiency with which those nucleic acid molecules are transcribed, theefficiency with which the resultant transcripts are translated, and theefficiency of post-translational modifications. Recombinant techniquesuseful for increasing the expression of nucleic acid molecules of thepresent invention include, but are not limited to, operatively linkingnucleic acid molecules to high-copy number plasmids, integration of thenucleic acid molecules into one or more host cell chromosomes, additionof vector stability sequences to plasmids, substitutions ormodifications of transcription control signals (e.g., promoters,operators, enhancers), substitutions or modifications of translationalcontrol signals (e.g., ribosome binding sites, Shine-Dalgarnosequences), modification of nucleic acid molecules of the presentinvention to correspond to the codon usage of the host cell, deletion ofsequences that destabilize transcripts, and use of control signals thattemporally separate recombinant cell growth from recombinant enzymeproduction during fermentation. The activity of an expressed recombinantantigen of the present invention may be improved by fragmenting,modifying, or derivatizing a nucleic acid molecule encoding such anantigen.

[0042] Recombinant antigens of the present inventions can be produced ina variety of ways known to those skilled in the art. In one embodiment,a recombinant antigen of the present invention is produced by culturinga cell capable of expressing the antigen under conditions effective toproduce the antigen, and recovering the antigen. A preferred cell toculture is a recombinant cell of the present invention. Effectiveculture conditions include, but are not limited to, effective media,bioreactor, temperature, pH and oxygen conditions that permit proteinproduction. An effective, medium refers to any medium in which a cell iscultured to produce a recombinant antigen of the present invention. Suchmedium typically comprises an aqueous medium having assimilable carbon,nitrogen and phosphate sources, and appropriate salts, minerals, metalsand other nutrients, such as vitamins. Recombinant cells of the presentinvention can be cultured in conventional fermentation bioreactors,shake flasks, test tubes, microtiter dishes, and petri plates. Culturingcan be carried out at a temperature, pH and oxygen content appropriatefor a recombinant cell. Such culturing conditions are within theexpertise of one of ordinary skill in the art. Examples of suitableconditions are included in the Examples section.

[0043] Depending on the vector and host system used for production, theexpressed recombinant antigens may either remain within the recombinantcell; be secreted into the fermentation medium; be secreted into a spacebetween two cellular membranes, such as the periplasmic space in E.coli; or be retained on the outer surface of a cell or viral membrane.

[0044] The phrase “recovering the antigen”, as well as similar phrases,refers to collecting the whole fermentation medium containing therecombinant product and need not imply additional steps of separation orpurification. Proteins of the present invention can be purified using avariety of standard protein purification techniques, such as, but notlimited to, affinity chromatography, ion exchange chromatography,filtration, electrophoresis, hydrophobic interaction chromatography, gelfiltration chromatography, reverse phase chromatography, Concanavalin Achromatography, chromatofocusing and differential solubilization.Recombinant antigens of the present invention are preferably retrievedin “substantially pure” form. As used herein, “substantially pure”refers to a purity that allows for the effective use of the protein as adetection reagent. Preferably, such a recombinant antigen reagent doesnot cause false positive reactions. In a preferred embodiment,recombinant antigens of the present invention are at least about 60%pure, preferably at least about 65% pure, more preferably at least about70% pure, more preferably at least about 75% pure, more preferably atleast about 80% pure, more preferably at least about 85% pure, morepreferably at least about 90% pure, and more preferably at least about95% pure. In one embodiment, a recombinant antigen of the presentinvention is at least about 98% to 100% pure.

[0045] One embodiment of the present invention is a method to determinethe immune status of an animal to a desired infectious agent bydetecting antibodies in that animal that selectively bind to thatinfectious agent. The method includes the steps of: (a) contacting abiological specimen of the animal with a recombinant infectious agentantigen that is specific for detecting an antibody selective for thatinfectious agent, under conditions suitable for formation of a complexbetween the recombinant antigen and the antibody; and (b) detecting thepresence or absence of the complex, wherein presence or absence of acomplex is indicative of the immune status of the animal. Presence of acomplex indicates that an animal is protected from, or is notsusceptible to, infection by that infectious agent, and as such, thatanimal need not be vaccinated. Absence of a complex suggests that ananimal may not be protected from, or may be susceptible to, infection bythat infectious agent, and as such, it is desirable to vaccinate thatanimal.

[0046] Antibodies to be detected can be maternal antibodies transferredto the offspring or can be generated (i.e., produced) in response to anatural infection by an infectious agent or vaccination. Vaccination canbe accomplished in a variety of ways known to those skilled in the artincluding, but not limited to, administering the infectious agent itselfor any immunogenic form thereof, such as, but not limited to, a modifiedlive infectious agent, an inactivated, disrupted, fractionated orattenuated infectious agent, a native or recombinant antigen, or anucleic acid molecule that invokes an immune response against theinfectious agent. Antibodies to be detected can be of any class, i.e.,immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE),immunoglobulin G (IgG), or immunoglobulin M (IgM) antibodies IgE, IgG,or IgM antibodies. Preferred antibodies to detect are IgA, IgG and IgMantibodies.

[0047] Any animal that possesses maternal antibodies or generatesantibodies in response to an infectious agent or corresponding vaccinecan be tested in accordance with the present invention. In oneembodiment, a preferred animal to test is an animal that was vaccinated(i.e., administered a vaccine) at least about six months, one year, twoyears, or three years prior to testing. In another embodiment, apreferred animal to test is an animal for whom infection or vaccinationstatus is unknown. Suitable animals for whom to determine an immunestatus include, but are not limited to, cats (i.e., felids), dogs (i.e.,canids), horses (i.e., equids), humans and other primates, ferrets andother Mustelids, cattle, sheep, swine, and rodents, as well as othercompanion animals (i.e., pets), food animals, work animals, or zooanimals. Preferred animals to test include cats, dogs, horses and othercompanion animals, with cats, dogs and horses being even more preferred.As used herein, a cat refers to any member of the cat family (i.e.,Felidae), including domestic cats, wild cats and zoo cats. Examples ofcats include, but are not limited to, domestic cats, lions, tigers,leopards, panthers, cougars, bobcats, lynx, jaguars, cheetahs, andservals. A preferred cat to test is a domestic cat. As used herein, adog refers to any member of the family Canidae, including, but notlimited to, domestic dogs, wild dogs, foxes, wolves, jackals, andcoyotes and other members of the family Canidae. As used herein, a horserefers to an equid. An equid is a hoofed mammal and includes, but is notlimited to, domestic horses and wild horses, such as, horses, asses,donkeys, and zebras. Preferred horses to test include domestic horses,including race horses.

[0048] A biological specimen refers to any sample that can be collected(i.e. obtained) from an animal in which antibodies may be found. Asuitable biological specimen includes, but is not limited to, a bodilyfluid composition or a cellular composition. Examples of a bodily fluidinclude, but are not limited to, blood, serum, plasma, saliva, urine,tears, aqueous humor, cerebrospinal fluid, lymph, nasal secretion,tracheobronchial aspirate, milk, colostrum, intestinal secretion, andfeces, with blood, serum, plasma, saliva, urine, tears, milk andcolostrum being preferred and blood, serum or plasma being even morepreferred.

[0049] As used herein, the term contacting refers to combining ormixing, in this case, a biological specimen and a recombinant antigen ofthe present invention. Formation of a complex, or immunocomplex, betweena recombinant antigen and any antibody selective for an infectious agent(i.e., an anti-infectious agent antibody) present in the biologicalspecimen refers to the ability of the recombinant antigen to selectivelybind to the antibody in order to form a stable complex that can bedetected. As used herein, the term selectively binds to an antibody orspecific for an antibody refers to the ability of a recombinant antigenof the present invention to preferentially bind to an antibody thatindicates that the animal is protected from disease, without being ableto substantially bind to other, unrelated, antibodies. Binding betweenthe recombinant antigen and anti-infectious agent antibody is effectedunder conditions suitable to form a complex; such conditions (e.g.,appropriate concentrations, buffers, temperatures, reaction times) aswell as methods to optimize such conditions are known to those skilledin the art, and examples are disclosed herein. Examples of complexformation conditions are also disclosed in, for example, in Sambrook etal., ibid., and Harlow, et al., 1988, Antibodies, a Laboratory Manual,Cold Spring Harbor Labs Press; Harlow et al., ibid., in incorporatedherein by reference in its entirety.

[0050] As used herein, the phrase detecting the presence or absence of acomplex refers to determining if any complex is formed, i.e., assayingfor the presence (i.e., existence) or absence (i.e., non-existence) of acomplex. If complexes are formed, the amount of complexes formed can,but need not be, determined. Complex formation, or selective binding,between a recombinant antigen and anti-infectious agent antibody can bemeasured (i.e., detected, determined) using a variety of methodsstandard in the art; see, for example, Sambrook, et al., ibid., Harlow,et al., ibid., and examples herein.

[0051] A complex can be measured in a variety of ways including, but notlimited to, one of the following assays: an enzyme-linked immunoassay, aradioimmunoassay, a fluorescence immunoassay, a luminescence assay (suchas a chemi-luminescent assay or a bio-luminescent assay), aphosphorescence assay, an immunoblot assay (e.g., a Western blot), animmunodot assay, an immunoprecipitation assay, a lateral flow assay, aflow-through assay, an agglutination assay, a particulate-based assay(e.g., using particulates such as, but not limited to, magneticparticles or plastic polymers, such as latex or polystyrene beads), andan electronic sensory assay (e.g., using an electronic chip). In oneembodiment, it is preferred not to use a virus neutralization assay, ahemagglutination assay, or a complement fixation assay. Such assays arewell known to those skilled in the art; see for, example, Harlow, etal., ibid. Assays can be used to give qualitative or quantitativeresults depending on how they are used.

[0052] Some assays, such as agglutination, particulate separation, andimmunoprecipitation, can be observed visually (e.g., either by eye or bya machines, such as a densitometer or spectrophotometer) without theneed for a detectable marker. In other assays, conjugation (i.e.,attachment, joining) of a detectable marker to a recombinant antigen ofthe present invention or to an antibody-binding partner of the presentinvention that selectively binds to the antibody being detected aids inmeasuring complex formation. Conjugation is conducted in such a mannerthat the ability of a recombinant antigen or antibody-binding partner toselectively bind to anti-infectious agent antibodies is not compromised.Conjugation can be accomplished, for example, by joining a detectablemarker to a recombinant antigen or antibody-binding partner or byconstructing a genetic chimera that encodes a recombinant antigen fusedto a detectable marker or an antibody-binding partner fused to adetectable marker.

[0053] Examples of detectable markers include, but are not limited to,an enzyme, a radioactive label, a fluorescent label, a luminescent label(e.g., a bioluminescent label or a chemi-luminescent label), achromophoric (e.g., calorimetric) label, a metal sol label, ametal-binding label, a physical label, an electronic label, or a ligand.A ligand refers to a molecule that binds selectively to anothermolecule. Preferred detectable markers include, but are not limited to,a phosphatase (e.g., alkaline phosphatase), a peroxidase (e.g.,horseradish peroxidase), a beta-galactosidase, a luciferase,fluorescein, a radioisotope, a bead (e.g., a color bead, a magneticbead), colloidal gold, biotin, avidin, and biotin-related compounds oravidin-related compounds (e.g., streptavidin or ImmunoPure®NeutrAvidin).

[0054] An antibody-binding partner of the present invention is anycompound that can bind to an anti-infectious agent antibody of thepresent invention. Preferably an antibody-binding partner binds to theconstant region of such an antibody, such as to the Fc region of an IgA,IgD, IgE, IgG, or IgM antibody. Examples of such antibody-bindingpartners include anti-isotype antibodies (e.g., anti-IgA antibodies,anti-IgD antibodies, anti-IgE antibodies, anti-IgG antibodies, andanti-IgM antibodies) that selectively bind to the constant region ofantibodies of the animal being tested, antibody Fc receptors (e.g., IgAreceptors, IgD receptors, IgE receptors, IgG receptors, IgM receptors),antibody-binding bacterial surface proteins (e.g., Protein A or ProteinG, or recombinant forms of these proteins), antibody-binding cells(e.g., a B cell, T cell, or a macrophage), other antibody-bindingeukaryotic cell surface proteins, and antibody-binding complementproteins, as well as any portion of these proteins that selectively bindto an anti-infectious agent antibody. Preferred antibody-bindingpartners include Protein A, Protein G, an anti-IgG antibody, an anti-IgMantibody, an anti-IgA antibody, an anti-IgE antibody, an Fc_(γ) receptormolecule, an Fc_(ε) receptor molecule, an Fc_(μ) receptor molecule, andan Fc receptor molecule as well as any portion of any of such proteinsthat selectively bind to the constant region of an anti-infectious agentantibody. It is within the scope of the present invention that a complexbetween an anti-infectious agent antibody and a recombinant antigen ofthe present invention can be determined using one or more layers and/ortypes of secondary antibodies or other binding compounds. For example,an unlabeled secondary antibody can be bound to an anti-infectious agentantibody and the unlabeled secondary antibody can then be bound by alabeled tertiary antibody.

[0055] In one embodiment of the present invention, the presence orabsence of a complex is detected by applying a detection reagent thatbinds to the complex, if present, to obtain a test signal. The termapplying refers to adding a detection reagent to the biological specimenafter the recombinant antigen is combined with the specimen underconditions to form a complex with any anti-infectious agent antibody inthe specimen. The detection reagent binds to any complex present andsuch binding results in a test signal, i.e., an event that can bedetected. If anti-infectious agent antibody is present in the biologicalspecimen, a test signal will ensue. If there is no anti-infectious agentantibody present, no test signal will occur. Preferably, the detectionreagent comprises an antibody-binding partner of the present inventionconjugated to a detectable marker of the present invention.

[0056] In one embodiment a complex can be formed and measured insolution. In another embodiment, a recombinant antigen of the presentinvention or an antibody-binding partner of the present invention can beimmobilized on (e.g., coated onto) a substrate. Preferably, arecombinant antigen of the present invention is immobilized on asubstrate. Immobilization techniques are known to those skilled in theart. Suitable substrates on which to immobilize a recombinant antigen orantibody-binding partner of the present invention or a compositioninclude, but are not limited to, plastic, glass, gel, celluloid, paper,fabric, electronic chip, and particulate materials such as latex,polystyrene, nylon, nitrocellulose, agarose, cotton, PVDF(poly-vinylidene-fluoride), and magnetic resin. Suitable substratesinclude, but are not limited to, a well (e.g., microtiter dish well), aplate, a dipstick, a strip, a bead, a sponge, a lateral flow apparatus,a membrane, a filter, a tube, a dish, a celluloid-type matrix, amagnetic particle, an electronic sensory device (e.g., an electronicsensory chip), and other particulates. In one embodiment, a substrate,such as a particulate, can include a detectable marker.

[0057] In a preferred embodiment, a method to determine the immunestatus of an animal can be conducted within about one day, morepreferably within about two hours, more preferably within about onehour, and even more preferably within a time period of between about oneminute and about fifteen minutes.

[0058] A method of the present invention to detect immune status can bequalitative, quantitative, or semi-quantitative. In one embodiment, themethod includes a step of comparing the intensity of a test signal ofthe present invention with a reference signal obtained by contacting areference reagent with the detection reagent to determine the amount ofanti-infectious agent antibody in the biological specimen. In oneembodiment, the reference signal represents a threshold, such that ifthe test signal is more intense than the reference signal the animalfrom which the biological specimen is collected is deemed to beprotected from infection by the infectious agent. In one embodiment thereference reagent is immobilized on a substrate, preferably on the samesubstrate as is a recombinant antigen. Suitable reference reagentsinclude antibodies isolated from the same species of animal as is beingtested. Preferred reference reagents to use in immune status assays forcats, dogs and horses, include feline antibodies, canine antibodies andequine antibodies, respectively.

[0059] One embodiment of a method of the present invention to determinethe immune status of an animal is to determine the immune status withrespect to more than one infectious agent. It is contemplated that anynumber of recombinant antigens can be used in such a determination. Inone embodiment, a biological specimen from an animal is contacted with arecombinant calicivirus antigen, a recombinant herpesvirus antigen and arecombinant parvovirus antigen under conditions such that the immunestatus of the animal to calicivirus, herpesvirus and parvovirusinfection is determined.

[0060] Another embodiment of the present invention includes the use ofan immune status assay to determine whether a human should be treatedfor rabies virus infection. In such an embodiment, a biological specimenis collected from an animal suspected of having exposed the human torabies virus infection and contacted with a recombinant rabies virusantigen in accordance with the present invention. Presence of a complexindicates that the human should be treated for rabies infection.

[0061] A preferred method to detect anti-infectious agent antibodies isan immunosorbent assay. In one embodiment, a recombinant antigen of thepresent invention is immobilized on a substrate, such as a microtiterdish well or a dipstick. A biological specimen collected from an animalis applied to the substrate and incubated under conditions sufficient toallow for complex formation. Excess fluid, if any, is removed and adetection reagent that can selectively bind to the anti-infectious agentantibody is added to the substrate and incubated to allow formation of acomplex between the detection reagent and the recombinantantigen:anti-infectious agent antibody complex. Excess detection reagentis removed, a developing agent is added if required, and the substrateis submitted to a detection device for analysis. Alternatively, anantibody-binding partner as described above is immobilized on asubstrate, and a biological specimen is incubated with theantibody-binding partner to form a complex. Complex detection can thenbe accomplished by applying a detectable marker-conjugated recombinantantigen of the present invention to the complex.

[0062] Another preferred method to determine the immune status of ananimal is a lateral flow assay, examples of which are disclosed in U.S.Pat. No. 5,424,193, issued Jun. 13, 1995, by Pronovost et al.; U.S. Pat.No. 5,415,994, issued May 16, 1995, by Imrich et al; WO 94/29696,published Dec. 22, 1994, by Miller et al.; and WO 94/01775, publishedJan. 20, 1994, by Pawlak et al.; each of these patent publications isincorporated by reference herein in its entirety. Another preferredmethod to determine the immune status of an animal is a flow-throughassay, examples of which are disclosed in U.S. Pat. No. 4,632,901,issued Dec. 30, 1986 by Valkirs et al., and U.S. Pat. No. 4,727,019,issued Feb. 23, 1988, by Valkirs et al; U.S. Pat. No. 4,632,901, ibid.,and U.S. Pat. No. 4,727,019, ibid., are both incorporated by referenceherein in their entireties.

[0063] Another embodiment of the present invention is a method todetermine whether to vaccinate an animal. Such a method includes thesteps of: (a) contacting a biological specimen of the animal with arecombinant infectious agent antigen that is specific for detecting anantibody selective for that infectious agent, under conditions suitablefor formation of a complex between the recombinant antigen and theantibody; and (b) detecting the presence or absence of the complex.Presence of such a complex indicates that the animal need not bevaccinated, whereas absence of such a complex indicates that the animalshould be vaccinated. Detection of such a complex can be accomplished ina manner similar to that disclosed herein for determining the immunestatus of an animal.

[0064] Yet another embodiment of the present invention is an assay, orkit, to determine the immune status of an anima and/or to determinewhether to vaccinate an animal. Such an assay includes (a) a recombinantinfectious agent antigen that is specific for detecting an antibodyselective for that infectious agent; and (b) a means to detect anantibody that selectively binds to the recombinant antigen. In oneembodiment, the means includes a detection reagent of the presentinvention. An assay of the present invention can also, but need not,include (a) a solid support comprising a test area and a reference area;and (b) a reference reagent. Preferably the test area includes one ormore recombinant antigens of the present invention and the referencearea comprises one or more reference reagents of the present invention.An assay of the present invention can also, but need not, include acontrol area for assay validation. Preferably, a recombinant infectiousagent antigen of the present invention is immobilized on a substratesuch as those disclosed herein. Particularly preferred assays areELISAs, lateral flow assays, and flow-through assays.

[0065] The following examples are provided for the purposes ofillustration and are not intended to limit the scope of the presentinvention.

EXAMPLES

[0066] It is to be noted that the Examples include a number of molecularbiology, microbiology, immunology and biochemistry techniques consideredto be known to those skilled in the art. Disclosure of such techniquescan be found, for example, in Sambrook et al., ibid., Harlow et al.,ibid., and related references.

Example 1

[0067] This Example demonstrates that use of a whole virus preparationto determine the immune status of an animal leads to false positivesand, as such, is an unacceptable reagent.

[0068] A. Purification of Feline Calicivirus and Feline RhinotracheitisVirus

[0069] Feline rhinotracheitis virus (also known as feline herpesvirus,or FHV) and feline calicivirus (FCV) were cultured in Crandall ReeseFeline Kidney (CRFK) cells in DMEM high glucose (available from GibcoBRL, Gaithersburg, Md.) with 2% fetal bovine serum (FBS) for FHV and nofetal bovine serum for FCV. Aliquots of titered (TCID₅₀)virus-containing tissue culture supernatant were collected and stored at−70° C. until use.

[0070] FCV- or FHV-containing supernatant aliquots were each thawedquickly in a 37° C. water bath and clarified by centrifugation at 1000×gfor 10 min at 4° C. Five volumes of a 60% (w/v) Iodixanol solution(available from OptiPrepä, Nycomed, Oslo, Norway) were mixed with onevolume of 0.8% NaCl, 60 mM HEPES, pH 7.4 to produce a 50% Iodixanolsolution. Three ml of the lodixanol-containing supernatant aliquot weretransferred to 16×102 mm Beckman Ultra Clear centrifuge tubes (availablefrom Beckman, Fullerton, Calif.). Three ml of the 50% Iodixanol solutionwere underlayed under the supernatant aliquot. The virus was sedimentedby centrifugation at 100,000×g for 1 hr at 4° C. using a Beckman SW28fixed-angle rotor (available from Beckman). The virus formed a sharpband on top of the lodixanol cushion. Three ml of the supernatant wereremoved. The residual content of the tube was mixed to produce aconcentrated virus suspension in approximately 25% lodixanol. Thesuspension was transferred to 16×76 mm Beckman Quickseal tubes(available from Beckman). The residual air space in the heat seal tubeswas filled with the 0.8% NaCl, 60 mM HEPES buffer and the tubes heatsealed. The tubes were centrifuged at 350,000×g for 1 to 3 hr at 4° C.using a Beckman VTi-65.1 rotor (available from Beckman). The rotor wasallowed to decelerate from 21×g (500 rpm) without the brake. The sealson the tubes were ruptured, and most of the supernatant was removed witha long Pasteur pipette. Approximately 1 ml of fluid was left in eachtube. This material was transferred to a common tube and the originaltube was rinsed with 0.5 ml of 0.8% NaCl/60 mM HEPES buffer and thatmaterial was added to the common tube. Total protein was determined bythe BioRad Protein Assay (available from BioRad, Richmond, Calif.).Aliquots of virus were stored at −70° C. Preparation purity wasdetermined by ELISA. FCV purified in this manner is referred to as anOptiprep-purified FCV preparation, or Optiprep-purified FCV. FHVpurified in this manner is referred to as an Optiprep-purified FHVpreparation, or Optiprep-purified FHV.

[0071] B. Purification of Feline Panleukopenia Virus

[0072] Feline panleukopenia virus (FPV) was cultured in Crandall ReeseFeline Kidney (CRFK) cells in DMEM high glucose with 2% fetal bovineserum. Aliquots of titered (TCID₅₀) virus-containing tissue culturesupernatant were collected and stored at −70° C. until use.

[0073] A FPV-containing supernatant aliquot was clarified bycentrifugation at 7000×g for 15 min at 4° C. The pellet was discardedand virus was precipitated from the supernatant by the addition of solidpolyethylene glycol (PEG) 3350 to 0.75 M PEG, and 0.2 M sodium chloride.The mixture was incubated 30 min on ice and then centrifuged at 7000×gfor 30 min at 4° C. The pellet was resuspended in 0.2 M boric acidbuffer (pH 7.4) with 0.5M NaCl. The material was centrifuged at 450×gfor 5 min to remove insoluble matter. The virus was banded in anisopyknic cesium chloride (CsCl) gradient (1.40 g/ml) by equilibriumcentrifugation at 150,000×g for 20 hr at 4° C. (40,000 rpm in BeckmanSW65 Ti rotor). Total protein was determined by the BioRad ProteinAssay. Aliquots of virus were stored at −70° C. Preparation purity wasdetermined by ELISA. FPV purified in this manner is referred to as aCsCl-purified FPV preparation, or CsCl-purified FPV.

[0074] C. Testing of a Whole FCV Preparation as an Immune Status Reagent

[0075] A Optiprep-purified FCV preparation, produced as described inExample 1A, as well as a preparation prepared in the same manner but inwhich CRFK cells were not infected with FCV (i.e., an Optiprep-purifiednon-infected cell, or NIC, preparation) was each tested for its abilityto react with serum from FCV-vaccinated (positive) cats or barriercontrol (negative) cats by ELISA.

[0076] The ELISA was conducted as follows. The Optiprep-purified FCV andNIC preparations were each diluted according to protein concentration asindicated in Table 1 into 50 mM carbonate/bicarbonate buffer (pH 9.6).After dilution, plates were coated with a 100-μL aliquot of eachdilution in wells in a PolySorp strip (Nunc, available from VWRScientific, West Chester, Pa.). Each strip was placed in a strip holderplate and incubated overnight at 4° C. The coated wells were washed fourtimes with PBST (10 mM PBS, containing 8.5 g NaCl, 0.20 g KH₂PO₄, and1.16 g Na₂HPO₄ in 1L water, at pH=7.2, 0.05% Tween-20 (C₅₈H₁₁₄O₂₆;FW=1227, available from Fisher Scientific, Pittsburgh, Pa.), using anautomatic plate washer (available from Bio-tek Instruments, Inc.,Winooski, Vt.). After washing, a 200-μL aliquot of StabilCoat (availablefrom SurModics, Eden Prairie, Minn.) was added to each well and thestrips were incubated for one hour at 22° C. The wells were then washedfour times with PBST using an automatic plate washer. Vaccinated(positive) or barrier (negative) cat serum was diluted 1:50 prior toaddition to the wells with diluent A (PBST, 4% FBS, 0.5% ProClin 300(available from Supelco, Bellefonte, Pa.). A 100-μL aliquot of theappropriate diluted serum was then added to each of the appropriatewells, and the plate was incubated for two hours at 22° C., followed byfour washes with PBST using an automatic plate washer. Goat anti-cat IgG(H & L)-HRP (available from Kirkegaard & Perry Laboratories,Gaithersburg, Md.) was diluted in diluent A to 500 ng/ml, and a 100-μLaliquot was then added to each well. The plates were incubated for onehour at 22° C., followed by four washes with PBST using an automaticplate washer. A 100-μL aliquot of two-component substrate (TMBPeroxidase Substrate System, available from Kirkegaard & PerryLaboratories) was added to each of wells, which were then incubated at22° C. for 5 min. Reactions were stopped by adding 100 μL of 1 M H₃PO₄to each of the wells, at which time an automatic plate reader was usedto determine O.D at 450 nm (using, for example, Molecular DevicesSpectraMax 250, available from Molecular Devices, Sunnyvale, Calif.).ELISA results are shown in Table 1. TABLE 1 ELISA usingOptiprep-purified FCV or NIC to test serum collected from FCV-vaccinated(positive) or barrier (negative) cats protein positive negative positivenegative (ng/ml) (FCV) (FCV) (NIC) (NIC) 20000 4.15 0.61 10000 4.15 0.703.368 0.616 5000 4.15 0.88 3.231 0.506 2500 4.15 0.84 2.901 0.396 12504.15 0.86 2.485 0.362 625 4.15 0.74 2.035 0.303 313 4.04 0.66 1.5860.264 156 4.00 0.62 1.204 0.244 78 3.72 0.52 0.782 0.216 39 3.22 0.450.721 0.165 20 2.68 0.36 0.629 0.134 10 2.34 0.36 0.598 0.124 5 2.160.31 0.653 0.13

[0077] These data indicate that although an Optiprep-purified FCVpreparation can detect antibodies in FCV-vaccinated cats, so does anOptiprep-purified NIC preparation (i.e., a preparation produced fromuninfected cells using a similar procedure). As such, whole FCV is anunacceptable reagent for the determination of the immune status of a catdue to the possibility of a high percentage of false positive reactionsdue to the presence of cellular proteins that react with serum fromvaccinated cats.

[0078] D. Testing of a Whole FHV Preparation as an Immune Status Reagent

[0079] A Optiprep-purified FHV preparation, produced as described inExample 1A, as well as a preparation prepared in the same manner but inwhich CRFK cells were not infected with FHV (i.e., an Optiprep-purifiednon-infected cell, or NIC, preparation) was each tested for its abilityto react with serum from FHV-vaccinated (positive) cats or barriercontrol (negative) cats by ELISA.

[0080] The ELISA was conducted as described in Example 1C except that anOptiprep-purified FHV preparation was used instead of anOptiprep-purified FCV preparation, serum from FHV-vaccinated cats wasused, and preparation dilutions were conducted as indicated in Table 2.Results are shown in Table 2. TABLE 2 ELISA using Optiprep-purified FHVor NIC to test serum collected from FHV-vaccinated (positive) or barrier(negative) cats protein positive negative positive negative (ng/ml)(FHV) (FHV) (NIC) (NIC) 20000 4.13 0.02 10000 4.13 0.02 3.368 0.616 50004.15 0.00 3.231 0.506 2500 4.14 0.01 2.901 0.396 1250 4.01 0.13 2.4850.362 625 3.73 0.37 2.035 0.303 313 3.47 0.46 1.586 0.264 156 2.95 0.401.204 0.244 78 2.25 0.47 0.782 0.216 39 1.68 0.38 0.721 0.165 20 1.400.50 0.629 0.134 10 0.80 0.26 0.598 0.124 5 0.72 0.17 0.653 0.13

[0081] These data indicate that although an Optiprep-purified FHVpreparation can detect antibodies in FHV-vaccinated cats, so does anOptiprep-purified NIC preparation (i.e., a preparation produced fromuninfected cells using a similar procedure). As such, whole FHV is anunacceptable reagent for the determination of the immune status of a catdue to the possibility of a high percentage of false positive reactionsdue to the presence of cellular proteins that react with serum fromvaccinated cats.

[0082] E. Testing of a Whole FPV Preparation as an Immune Status Reagent

[0083] A CsCl-purified FPV preparation, produced as described in Example1B, as well as a preparation prepared in the same manner but in whichCRFK cells were not infected with FPV (i.e., a CsCl-purifiednon-infected cell, or NIC, preparation) was each tested for its abilityto react with serum from FPV-vaccinated (positive) cats or barriercontrol (negative) cats by ELISA.

[0084] The ELISA was conducted as described in Example 1C except that aCsCl-purified FPV preparation was used instead of an Optiprep-purifiedFCV preparation, serum from FPV-vaccinated cats was used, andpreparation dilutions were conducted as indicated in Table 3. Resultsare shown in Table 3. TABLE 3 ELISA using CsCl-purified FPV or NIC totest serum collected from FPV-vaccinated (positive) or barrier(negative) cats protein positive negative positive negative (ng/ml)(FPV) (FPV) (NIC) (NIC) 10000 4.082 0.468 3.368 0.616 5000 4.031 0.4743.231 0.506 2500 3.947 0.492 2.901 0.396 1250 3.799 0.5 2.485 0.362 6253.233 0.481 2.035 0.303 313 2.58 0.393 1.586 0.264 156 1.929 0.287 1.2040.244 78 1.115 0.21 0.782 0.216 39 0.836 0.16 0.721 0.165 20 0.655 0.1340.629 0.134 10 0.752 0.111 0.598 0.124 5 0.527 0.103 0.653 0.13

[0085] These data indicate that although a CsCl-purified FPV preparationcan detect antibodies in FPV-vaccinated cats, so does a CsCl-purifiedNIC preparation (i.e., a preparation produced from uninfected cellsusing a similar procedure). As such, whole FPV is an unacceptablereagent for the determination of the immune status of a cat due to thepossibility of a high percentage of false positive reactions due to thepresence of cellular proteins that react with serum from vaccinatedcats.

Example 2

[0086] This Example describes the isolation and expression of nucleicacid molecules of the present invention that encode feline caliciviruscoat proteins (FCVCPs) of the present invention. Also described is thepurification of recombinant feline calicivirus coat proteins (rFCVCPs)of the present invention.

[0087] A. A nucleic acid molecule of 2016 nucleotides designated hereinas nFCVCP₂₀₁₃ with a coding strand represented by SEQ ID NO:1, encodinga full-length FCVCP, was produced by PCR amplification and TA cloningusing standard techniques, such as those described in Sambrook et al.,ibid. Nucleic acid molecule nFCVCP₂₀₁₃ was ligated to recombinant vectorλP_(R)cro/T² ori/RSET-B, described in PCT Publication No. WO 98/12563,published Mar. 26, 1998, by Grieve et al., in such a manner that thenucleotides of the recombinant vector encoding the N-terminal histidine(His) tag were ligated in frame with the nucleotides encoding the felinecalicivirus coat protein. The resulting recombinant molecule, designatedherein as pλP_(R)His-nFCVCP₂₀₁₃, was transformed into Escherichia colito produce recombinant cell E. coli:pλP_(R)His-nFCVCP₂₀₁₃ using standardtechniques, such as those disclosed in Sambrook et al., ibid.Recombinant cell E. coli:pλP_(R)His-nFCVCP₂₀₁₃ was cultured as describedin WO 98/12563, ibid., to produce a 672-amino acid FCVCP protein, havingSEQ ID NO:2, designated PFCVCP₆₇₁, fused to a His tag. The fusionprotein, referred to herein as PHis-PFCVCP₆₇₁, was purified from E. coliby standard protein purification techniques.

[0088] B. A nucleic acid molecule of 1644 nucleotides, designated hereinas nFCVCP₁₆₄₁ with a coding strand represented by SEQ ID NO:3, whichspans nucleotides 373 to 2016 of SEQ ID NO:1, encoding a mature FCVCP,was produced by PCR amplification and TA cloning as described in Example2A. Nucleic acid molecule nFCVCP₁₆₄₁ was ligated to recombinant vectorλP_(R)cro/T² ori/RSET-B/Hisless, a modified version of recombinantvector λPR cro/T² ori/RSET-B (described in Example 2A) from which codonsencoding the His tag had been removed. The resulting recombinantmolecule, designated herein as pλP_(R)-nFCVCP₁₆₄₁, was transformed intoEscherichia coli to produce recombinant cell E. coli:pλP_(R)-nFCVCP₁₆₄₁as described in Example 2A. Recombinant cell E. coli:pλP_(R)-nFCVCP₁₆₄₁was cultured as described in Example 2A WO 98/12563, ibid., to produce a548-amino acid FCVCP protein, designated PFCVCP₅₄₇, the amino acidsequence of which is represented herein as SEQ ID NO:4. PFCVCP₅₄₇ waspurified from E. coli by standard protein purification techniques.

Example 3

[0089] This Example describes the isolation and expression of nucleicacid molecules of the present invention that encode feline parvoviruscapsid proteins (FPVVPs) of the present invention. Also described is thepurification of recombinant feline parvovirus capsid proteins (rFPVVPs)of the present invention.

[0090] A. A nucleic acid molecule of 1755 nucleotides, designated hereinas nFPVVP2₁₇₅₂ with a coding strand represented by SEQ ID NO:5, encodinga full-length feline parvovirus VP2 capsid protein, was produced by PCRamplification and TA cloning as described in Example 2A. Nucleic acidmolecule nFPVVP2₁₇₅₂ was ligated to recombinant vector λP_(R)cro/T²ori/RSET-B as described in Example 2A to produce recombinant moleculepλP_(R)His-nFPVVP2₁₇₅₂, which was then transformed into Escherichia colito produce recombinant cell E. coli:pλP_(R)His-nFPVVP2₁₇₅₂ as describedin Example 2A. Recombinant cell E. coli:pλP_(R)His-nFPVVP2₁₇₅₂ wascultured as described in Example 2A to produce a 585-amino acid FPVVP2protein, having SEQ ID NO:6, designated PFPVVP2₅84, fused to a His tag.The fusion protein, referred to herein as PHis-PFPVVP2₅₈₄, was purifiedfrom E. coli by standard protein purification techniques.

[0091] B. A nucleic acid molecule of 729 nucleotides, designated hereinas nFPVVP2C₇₂₉ with a coding strand represented by SEQ ID NO:7, whichspans nucleotides 703 to 1431 of SEQ ID NO:5, encoding a truncated VP2capsid protein, was produced by PCR amplification and TA cloning asdescribed in Example 2A. Nucleic acid molecule nFPVVP2C₇₂₉ was ligatedto recombinant vector λP_(R)cro/T² ori/RSET-B as described in Example 2Ato produce recombinant molecule pλP_(R)His-nFPVVP2C₇₂₉, which was thentransformed into Escherichia coli to produce recombinant cell E.coli:pλP_(R)His-nFPVVP2C₇₂₉ as described in Example 2A. Recombinant cellE. coli:pλP_(R)His-nFPVVP2C₇₂₉ was cultured as described in Example 2Ato produce a 243-amino acid FPVVP2 protein, having SEQ ID NO:8,designated PFPVVP2C₂₄₃, fused to a His tag. The fusion protein, referredto herein as PHis-PFPVVP2C₂₄₃, was purified from E. coli by standardprotein purification techniques.

[0092] Nucleic acid molecule nFPVVP2C₇₂₉ was also ligated to recombinantvector λP_(R)cro/T² ori/RSET-B/Hisless as described in Example 2B toproduce recombinant molecule pλP_(R)-nFPVVP²C₇₂₉, which was thentransformed into Escherichia coli to produce recombinant cell E.coli:pλP_(R)-nFPVVP2C₇₂₉ as described in Example 2A. Recombinant cell E.coli:pλP_(R)-nFPVVP2C₇₂₉ was cultured as described in Example 2A toproduce a 243-amino acid FPVVP2 protein, designated herein asPFPVVP2C₂₄₃, the amino acid sequence of which is represented herein asSEQ ID NO:8. PFPVVP2C₂₄₃ was purified from E. coli by 10 standardprotein purification techniques.

[0093] C. A nucleic acid molecule of 1860 nucleotides, designated hereinas nFPVpVP12₁₈₆₀ with a coding strand represented by SEQ ID NO:9,encoding a truncated VP1-VP2 capsid protein, was produced by PCRamplification and TA cloning as described in Example 2A. Nucleic acidmolecule nFPVpVP12₁₈₆₀ was ligated to recombinant vector λP_(R)cro/T²ori/RSET-B as described in Example 2A to produce recombinant moleculepλP_(R)His-nFPVpVP12₁₈₆₀, which was then transformed into Escherichiacoli to produce recombinant cell E. coli:pλP_(R)His-nFPVpVP121860 asdescribed in Example 2A. Recombinant cell E.coli:pλP_(R)His-nFPVpVP12₁₈₆₀ was cultured as described in Example 2A toproduce a 620-amino acid FPVVP12 protein, having SEQ ID NO:10,designated PFPVpVP12₆₂₀, fused to a His tag. The fusion protein,referred to herein as PHis-PFPVpVP12₆₂₀, was purified from E. coli bystandard protein purification techniques.

[0094] D. A nucleic acid molecule of 1431 nucleotides, designated hereinas nFPVpVP2₁₄₃₁ with a coding strand represented by SEQ ID NO:11, whichspans nucleotides 1 to 1431 of SEQ ID NO:5, encoding a truncated VP2capsid protein, was produced by PCR amplification and TA cloning asdescribed in Example 2A. Nucleic acid molecule nFPVpVP2₁₄₃₁ was ligatedto recombinant vector λP_(R)cro/T² ori/RSET-B/Hisless as described inExample 2B to produce recombinant molecule pλP_(R)-nFPVpVP2₁₄₃₁, whichwas then transformed into Escherichia coli to produce recombinant cellE. coli:pλP_(R)-nFPVpVP2₁₄₃, as described in Example 2A. Recombinantcell E. coli:pλP_(R)-nFPVpVP2₁₄₃₁, was cultured as described in Example2A to produce a 477-amino acid truncated FPVVP2 protein, designatedPFPVpVP2₄₇₇, the amino acid sequence of which is represented as SEQ IDNO:12. PFPVpVP2₄₇₇ was purified from E. coli by standard proteinpurification techniques.

[0095] Nucleic acid molecule nFPVpVP2₁₄₃₁ was also ligated torecombinant vector λP_(R)cro/T² ori/RSET-B as described in Example 2A toproduce recombinant molecule pλP_(R)His-nFPVpVP2₁₄₃₁, which was thentransformed into Escherichia coli to produce recombinant cell E.coli:pλP_(R)His-nFPVpVP2₁₄₃₁ as described in Example 2A. Recombinantcell E. coli:pλP_(R)His-nFPVpVP2₁₄₃₁ was cultured as described inExample 2A to produce a 477-amino acid truncated FPVVP2 protein,designated PFPVpVP2₄₇₇, with SEQ ID NO:12, fused to a His tag. Thefusion protein, designated PHis-PFPVpVP2₄₇₇ was purified from E. coli bystandard protein purification techniques.

Example 4

[0096] This Example describes the isolation and expression of nucleicacid molecules of the present invention that encode feline herpesvirusglycoproteins of the present invention. Also described is thepurification of recombinant feline herpesvirus glycoproteins (rFHVgB,rFHVgC, and rFHV gD proteins) of the present invention.

[0097] A. A nucleic acid molecule of 2832 nucleotides, designated hereinas nFHVgB₂₈₂₉ with a coding strand represented by SEQ ID NO:13, encodinga full-length feline herpesvirus glycoprotein B protein, was produced byPCR amplification and TA cloning as described in Example 2A. Nucleicacid molecule nFHVgB₂₈₂₉ was ligated to recombinant vector λP_(R)cro/T²ori/RSET-B as described in Example 2A to produce recombinant moleculepλP_(R)His-nFHVgB₂₈₂₉, which was then transformed into Escherichia colito produce recombinant cell E. coli:pλP_(R)His-nFHVgB₂₈₂₉ as describedin Example 2A. Recombinant cell E. coli:pλP_(R)His-nFHVgB₂₈₂₉ wascultured as described in Example 2A to produce a 944-amino acid FHVgBprotein, having SEQ ID NO:14, designated PFHVgB₉₄₃, fused to a His tag.The fusion protein, referred to herein as PHis-PFHVgB₉₄₃, was purifiedfrom E. coli by standard protein purification techniques.

[0098] B. A nucleic acid molecule of 750 nucleotides, designated hereinas nFHVgB₇₅₀ with a coding strand represented by SEQ ID NO:15, spanningnucleotides 1 to 750 of SEQ ID NO:13, encoding a truncated felineherpesvirus glycoprotein B protein, was produced by PCR amplificationand TA cloning as described in Example 2A. Nucleic acid moleculenFHVgB₇₅₀ was ligated to recombinant vector λP_(R)cro/T² ori/RSET-B asdescribed in Example 2A to produce recombinant moleculepλP_(R)His-nFHVgB₇₅₀, which was then transformed into Escherichia colito produce recombinant cell E. coli:pλP_(R)His-nFHVgB₇₅₀ as described inExample 2A. Recombinant cell E. coli:pλP_(R)His-nFHVgB₇₅₀ was culturedas described in Example 2A to produce a 250-amino acid FHVgB protein,having SEQ ID NO:16, designated PFHVgB₂₅₀, fused to a His tag. Thefusion protein, referred to herein as PHis-PFHVgB₂₅₀, was purified fromE. coli by standard protein purification techniques.

[0099] C. A nucleic acid molecule of 1605 nucleotides, designated hereinas nFHVgC₁₆₀₂ with a coding strand represented by SEQ ID NO:17, encodinga full-length feline herpesvirus glycoprotein C protein, was produced byPCR amplification and TA cloning as described in Example 2A. Nucleicacid molecule nFHVgC₁₆₀₂ was ligated to recombinant vector λP_(R)cro/T²ori/RSET-B as described in Example 2A to produce recombinant moleculepλP_(R)His-nFHVgC₁₆₀₂, which was then transformed into Escherichia colito produce recombinant cell E. coli:pλP_(R)His-nFHVgC₁₆₀₂ as describedin Example 2A. Recombinant cell E. coli:pλP_(R)His-nFHVgC₁₆₀₂ wascultured as described in Example 2A to produce a 535-amino acid FHVgCprotein, having SEQ ID NO:18, designated PFHVgC₅₃₄, fused to a His tag.The fusion protein, referred to herein as PHis-PFHVgC₅₃₄, was purifiedfrom E. coli by standard protein purification techniques.

[0100] D. A nucleic acid molecule of 1401 nucleotides, designated hereinas nFHVgC₁₄₀, with a coding strand represented by SEQ ID NO:19, spanningnucleotides 97 to 1497 of SEQ ID NO:17, encoding a truncated felineherpesvirus glycoprotein C protein was produced by PCR amplification andTA cloning as described in Example 2A. Nucleic acid molecule nFHVgC₁₄₀₁was ligated to recombinant vector λP_(R)cro/T² ori/RSET-B as describedin Example 2A to produce recombinant molecule pλP_(R)His-nFHVgC₁₄₀₁,which was then transformed into Escherichia coli to produce recombinantcell E. coli:pλP_(R)His-nFHVgC₁₄₀₁ as described in Example 2A.Recombinant cell E. coli:pλP_(R)His-nFHVgC₁₄₀₁, was cultured asdescribed in Example 2A to produce a 467-amino acid FHVgC protein,having SEQ ID NO:20, designated PFHVgC₄₆₇, fused to a His tag. Thefusion protein, referred to herein as PHis-PFHVgC₄₆₇, was purified fromE. coli by standard protein purification techniques.

[0101] E. A nucleic acid molecule of 1401 nucleotides, designatednFHVgC_(1401(opt)), encoding feline herpesvirus protein PFHVgC₄₆₇ but inwhich a number of codons were optimized for expression in E. coli wasproduced as follows. A series of PCR mutagenesis steps was performed onnFHVgC₁₄₀₁, the coding strand of which is represented by SEQ ID NO:19,using standard techniques, such as those described in Sambrook et al.,ibid., to target the following codons: two arginine codons spanningnucleotides 119 to 124 of SEQ ID NO:19; three serine codons spanningnucleotides 133 to 141 of SEQ ID NO:19; a glycine codon spanningnucleotides 724 to 726 of SEQ ID NO:19; and a leucine codon spanningnucleotides 727 to 729 of SEQ ID NO:19. The resulting nucleic acidmolecule, namely nFHVgC_(1401(opt)), has a coding strand sequence asrepresented in SEQ ID NO:21. Nucleic acid molecule nFHVgC_(1401(opt))was ligated to recombinant vector λP_(R)cro/T² ori/RSET-B/Hisless asdescribed in Example 2B to produce recombinant moleculepλP_(R)-nFHVgC_(1401(opt)), which was then transformed into Escherichiacoli to produce recombinant cell E. coli:pλP_(R)-nFHVgC_(1401(opt)) asdescribed in Example 2A. Recombinant cell E.coli:pλP_(R)-nFHVgC_(1401(opt)) was cultured as described in Example 2Ato produce a 467-amino acid FHVgC protein, designated PFHVgC_(467(opt)).PFHVgC_(467(opt)), the amino acid sequence of which is represented asSEQ ID NO:22, which is identical to SEQ ID NO:20, was purified from E.coli by standard protein purification techniques.

[0102] F. A nucleic acid molecule of 1125 nucleotides, designated hereinas nFHVgD₁₁₂₂ with a coding strand represented by SEQ ID NO:23, encodinga full-length feline herpesvirus glycoprotein D protein, was produced byPCR amplification and TA cloning as described in Example 2A. Nucleicacid molecule nFHVgD,₁₂₂ was ligated to recombinant vector λP_(R)cro/T²ori/RSET-B as described in Example 2A to produce recombinant moleculepλP_(R)His-nFHVgD₁₁₂₂, which was then transformed into Escherichia colito produce recombinant cell E. coli:pλP_(R)His-nFHVgD₁₂₂ as described inExample 2A. Recombinant cell E. coli:pXPRHis-nFHVgD₁₁₂₂ was cultured asdescribed in Example 2A to produce a 375-amino acid FHVgD protein,having SEQ ID NO:24, designated PFHVgD₃₇₄, fused to a His tag. Thefusion protein, referred to herein as PHis-PFHVgD₃₇₄, was purified fromE. coli by standard protein purification techniques.

[0103] G. A nucleic acid molecule of 900 nucleotides, designated hereinas nFHVgD₉₀₀ with a coding strand represented by SEQ ID NO:25, spanningnucleotides 85 to 894 of SEQ ID NO:23, encoding a truncated felineherpesvirus glycoprotein D protein, was produced by PCR amplificationand TA cloning as described in Example 2A. Nucleic acid moleculenFHVgD₉₀₀ was ligated to recombinant vector λP_(R)cro/T² ori/RSET-B asdescribed in Example 2A to produce recombinant moleculepkPRHis-nFHVgD₉₀₀, which was then transformed into Escherichia coli toproduce recombinant cell E. coli:pλP_(R)His-nFHVgD₉₀₀ as described inExample 2A. Recombinant cell E. coli:pλP_(R)His-nFHVgD₉₀₀ was culturedas described in Example 2A to produce a 300-amino acid FHVgD protein,having SEQ ID NO:26, designated PFHVgD₃₀₀, fused to a His tag. Thefusion protein, referred to herein as PHis-PFHVgD₃₀₀, was purified fromE. coli by standard protein purification techniques.

Example 5

[0104] This Example describes the isolation and expression of nucleicacid molecules of the present invention that encode feline leukemiavirus (FeLV) proteins of the present invention. Also described is thepurification of recombinant feline herpesvirus proteins (rFeLVp27 andrFeLVgp70 proteins) of the present invention.

[0105] A. A nucleic acid molecule of 789 nucleotides, designated hereinas nFeLVp27₇₅₉ with a coding strand represented by SEQ ID NO:27,encoding a mature FeLV p27 protein, was produced by PCR amplificationand TA cloning as described in Example 2A. Nucleic acid moleculenFeLVp27₇₅₉ was ligated to recombinant vector λP_(R)cro/T²ori/RSET-B/Hisless as described in Example 2B to produce recombinantmolecule pXPR-nFeLVp27₇₅₉, which was then transformed into Escherichiacoli to produce recombinant cell E. coli:pλP_(R)-nFeLVp27₇₅₉ asdescribed in Example 2A. Recombinant cell E. coli:pλP_(R)-nFeLVp27₇₅₉was cultured as described in Example 2A to produce a 263-amino acid FeLVp27 protein designated PFeLVp27₂₅₃, the amino acid sequence of which isrepresented as SEQ ID NO:28. PFeLVp27₂₅₃ was purified from E. coli bystandard protein purification techniques.

[0106] B. A nucleic acid molecule of 1857 nucleotides, designated hereinas nFeLVgp70₁₈₃₀ with a coding strand represented by SEQ ID NO:29,encoding a mature FeLV envelope glycoprotein 70 (gp70) protein, wasproduced by PCR amplification and TA cloning as described in Example 2A.Nucleic acid molecule nFeLVgp70₁₈₃₀ was ligated to recombinant vectorλP_(R)cro/T² ori/RSET-B as described in Example 2A to producerecombinant molecule pλP_(R)His-nFeLVp27₁₈₅₇, which was then transformedinto Escherichia coli to produce recombinant cell E.coli:pλP_(R)His-nFeLVp27₁₈₅₇ as described in Example 2A. Recombinantcell E. coli:pλP_(R)His-nFeLVp27₁₈₅₇ was cultured as described inExample 2A to produce a 619-amino acid FeLV gp70 protein designatedPFeLVgp70₆₁₀, the amino acid sequence of which is represented as SEQ IDNO:30, fused to a His tag. The fusion protein, referred to herein asPHis-PFeLVgp70₆₁₀, was purified from E. coli by standard proteinpurification techniques.

[0107] C. A nucleic acid molecule of 1833 nucleotides, designated hereinas nFeLVp27-gp70₁₈₃₃ with a coding strand represented by SEQ ID NO:31,encoding a fusion protein of the carboxy-terminus of FeLV Pr65-gag andgp70, was produced by PCR amplification and TA cloning as described inExample 2A. Nucleic acid molecule nFeLVp27-gp70₁₈₃₃ was ligated torecombinant vector λP_(R)cro/T² ori/RSET-B/Hisless as described inExample 2B to produce recombinant molecule pλPR-nFeLVp27-gp70₁₈₃₃ whichwas then transformed into Escherichia coli to produce recombinant cellE. coli:pλP_(R)-nFeLVp27-gp70₁₈₃₃ as described in Example 2A.Recombinant cell E. coli:pλP_(R)-nFeLVp27-gp70₁₈₃₃ was cultured asdescribed in Example 2A to produce a 611-amino acid fusion protein,designated as PFeLVp27-gp70₆₁₁, the amino acid sequence of which isrepresented as SEQ ID NO:32. PFeLVp27-gp70₆₁₁ was purified from E. coliby standard protein purification techniques.

[0108] Nucleic acid molecule nFeLVp27-gp70₁₈₃₃ was also ligated torecombinant vector λP_(R)cro/T² ori/RSET-B as described in Example 2B toproduce recombinant molecule pλP_(R)His-nFeLVp27-gp70₁₈₃₃ which was thentransformed into Escherichia coli to produce recombinant cell E.coli:pλP_(R)His-nFeLVp27-gp70₁₈₃₃ as described in Example 2A.Recombinant cell E. coli:pλP_(R)His-nFeLVp27-gp70₁₈₃₃ was cultured asdescribed in Example 2A to produce a 611-amino acid fusion protein,designated as PFeLVp27-gp70₆₁₁, the amino acid sequence of which isrepresented as SEQ ID NO:32, fused to a His tag. The fusion protein,designated PHis-PFeLVp27-gp70₆₁₁, was purified from E. coli by standardprotein purification techniques.

Example 6

[0109] This Example describes the isolation and expression of nucleicacid molecules of the present invention that encode canine distempervirus (CDV) proteins of the present invention. Also described is thepurification of recombinant CDV hemagglutinin (rCDVH) and fusion (rCDVF)proteins of the present invention.

[0110] A. A nucleic acid molecule of 1812 nucleotides, designated hereinas nCDVH₁₈₁₂ with a coding strand represented by SEQ ID NO:33, encodinga CDV hemagglutinin protein, was produced by PCR amplification and TAcloning as described in Example 2A. Nucleic acid molecule nCDVH₁₈₁₂ wasligated to recombinant vector λP_(R)cro/T² ori/RSET-B as described inExample 2A to produce recombinant molecule pλP_(R)His-nCDVH₁₈₁₂, whichwas then transformed into Escherichia coli to produce recombinant cellE. coli:pλP_(R)His-nCDVH₁₈₁₂ as described in Example 2A. Recombinantcell E. coli:pλP_(R)His-nCDVH₁₈₁₂ was cultured as described in Example2A to produce a 604-amino acid protein designated PCDVH₆₀₄, the aminoacid sequence of which is represented as SEQ ID NO:34, fused to a Histag. The fusion protein, designated PHis-PCDVH₆₀₄, was purified from E.coli by standard protein purification techniques.

[0111] B. A nucleic acid molecule of 1986 nucleotides, designated hereinas nCDVF₁₉₈₆ with a coding strand represented by SEQ ID NO:35, encodinga CDV fusion protein, was produced by PCR amplification and TA cloningas described in Example 2A. Nucleic acid molecule nCDVF₁₉₈₆ was ligatedto recombinant vector λP_(R)cro/T² ori/RSET-B as described in Example 2Ato produce recombinant molecule pλP_(R)His-nCDVF₁₉₈₆, which was thentransformed into Escherichia coli to produce recombinant cell E.coli:pλP_(R)His-nCDVF₁₉₈₆ as described in Example 2A. Recombinant cellE. coli:pλP_(R)His-nCDVF₁₉₈₆ was cultured as described in Example 2A toproduce a 662-amino acid protein designated PCDVF₆₆₂, the amino acidsequence of which is represented as SEQ ID NO:36, fused to a His tag.The fusion protein, designated PHis-PCDVF₆₆₂, was purified from E. coliby standard protein purification techniques.

Example 7

[0112] This Example demonstrates an immune status assay of the presentinvention. In particular, this Example demonstrates a correlationbetween humoral immune responses in cats previously vaccinated withpanleukopenia (FPV), herpesvirus 1 (FHV-1), and calicivirus (FCV)vaccines and protection of such cats from challenge infections.

[0113] Forty cats were treated in the following manner: 14 cats werevaccinated with FCV, FHV-1 and FPV vaccines once, 6 months prior tochallenge; 12 cats were vaccinated with FCV, FHV-1 and FPV vaccineseither once or twice, with the last vaccine given 30 to 36 months priorto challenge; and 14 cats were unvaccinated. Challenge was accomplishedfollowing USDA challenge protocols utilized for vaccine approval. Animmune status ELISA was utilized to determine the amounts of anti-FCVantibodies, anti-FHV antibodies, and anti-FPV antibodies in the serum ofeach of the cats prior to challenge using, respectively, the followingrecombinant antigens of the present invention: recombinant FCV coatprotein (rFCVCP) protein PFCVCP₅₄₇, the amino acid sequence of which isrepresented as SEQ ID NO:4, and the production of which is described inExample 2B; recombinant FHV glycoprotein C (rFHVgC) proteinPHis-PFHVgC₄₆₇, a fusion protein of FHVgC₄₆₇,the amino acid sequence ofwhich is represented by SEQ ID NO:22, the production of which isdescribed in Example 4D; and recombinant FPV VP2 capsid protein(rFPVVP2) protein PFPVpVP2₄₇₇, the amino acid sequence of which isrepresented as SEQ ID NO:12, and the production of which is described inExample 3D. Cutoff values were based on results from 30 unvaccinatedcats. ELISAs were conducted in a similar manner to those described inExample 1C, with the following modifications: The specified recombinantantigens were used to coat plates (100 μL per well) at the followingconcentrations: rFCVCP protein PFCVCP₅₄₇ (starting concentration of 3mg/ml) was diluted to 20 ng/ml (1:150,000 dilution); rFHVgC proteinPFHVgC₄₆₇ (starting concentration of 2.24 mg/ml) was diluted to 50 ng/ml(1:44,800); and rFPVVP2 protein PFPVpVP2₄₇₇ (starting concentration of1.12 mg/ml) was diluted to 120 ng/ml (1:9333). For wells containingrFCVCP and rFHVgC antigens, cat serum being tested was diluted 1:800 indiluent A; for wells containing rFPVVP2 antigen, the cat serum beingtested was diluted 1:100 with diluent A.

[0114] Antibody levels were compared to clinical scores (FCV, FHV-1) ordevelopment of neutropenia (FPV). Cats were considered protected againstFCV or FHV-1 if the clinical score was ≦50% of the mean of theunvaccinated cat group clinical score. Correlations between anti-FCV,anti-FHV and anti-FPV antibody levels and respective clinical scores forFCV, clinical scores for FHV-1, and development of neutropenia (FPV) areshown, respectively in Tables 4, 5, and 6. TABLE 4 Correlation betweenclinical scores after FCV challenge and anti-FCV antibody levelsmeasured by ELISA using recombinant antigen PFCVCP₅₄₇ Sample Group ODAve OD SD ELISA Clin Score 79 vaccine I 4.200 0.000 + 0 80 vaccine I4.200 0.000 + 1 93 vaccine I 4.200 0.000 + 5 100 vaccine I 4.200 0.000 +3 116 vaccine I 4.200 0.000 + 0 118 vaccine I 4.200 0.000 + 4 119vaccine I 4.200 0.000 + 1 122 vaccine I 4.200 0.000 + 0 123 vaccine I4.200 0.000 + 1 130 vaccine I 4.200 0.000 + 8 148 vaccine I 4.2000.000 + 0 155 vaccine I 4.200 0.000 + 2 156 vaccine I 4.200 0.000 + 07029 vaccine I 4.200 0.000 + 0 QVY3 vaccine II 4.200 0.000 + 2 AMI4vaccine II 4.200 0.000 + 0 AMX1 vaccine II 4.200 0.000 + 0 G444 vaccineII 4.200 0.000 + 0 BWN3 vaccine II 4.200 0.000 + 0 QWM3 vaccine II 4.2000.000 + 0 QVF3 vaccine II 4.200 0.000 + 0 G087 vaccine II 4.200 0.000 +0 3592 vaccine II 4.200 0.000 + 0 1959 vaccine II 4.200 0.000 + 2 AME5vaccine II 4.200 0.000 + 0 3513 vaccine II 4.200 0.000 + 0 7086 controlI − 7 7090 control I − 17 7113 control I − 19 7115 control I − 23 7122control I − 12 7123 control I − 27 7124 control I − 24 7131 control I −21 7132 control I − 34 7133 control I − 25 ALV3 control II − 44 ALT2control II − 35 ALV5 control II − 38 ALZ1 control II − 47 AIY2 negative0.447 0.213 − AIW5 negative 0.383 0.098 − AIY3 negative 0.514 0.255 −AIU5 negative 0.479 0.206 − AIW7 negative 0.463 0.094 − AIY2 negative0.345 0.090 − AIU4 negative 0.440 0.118 − AIW6 negative 0.389 0.071 −AIV1 negative 0.427 0.111 − AIW1 negative 0.307 0.098 − AIW3 negative0.299 0.104 − AIU3 negative 0.389 0.041 − AIW4 negative 0.368 0.197 −AIW2 negative 0.429 0.181 − AIY1 negative 2.370 1.125 + Neg. Ave 0.406Neg. SD 0.064 Ave + 2SD 0.533

[0115] TABLE 5 Correlation between clinical scores after FHV-1 challengeand anti-FHV antibody levels measured by ELISA using recombinant antigenPFHVgC₄₆₇ Sample Group OD Ave OD SD ELISA Clin Score 79 vaccine I 0.6120.238 +/− 1 80 vaccine I 0.823 0.219 + 12 93 vaccine I 0.412 0.152 − 38100 vaccine I 1.203 0.087 + 2 116 vaccine I 0.776 0.165 + 5 118 vaccineI 3.064 0.405 + 1 119 vaccine I 0.697 0.047 + 5 122 vaccine I 0.7020.148 + 7 123 vaccine I 0.929 0.134 + 4 130 vaccine I 1.291 0.352 + 14148 vaccine I 0.769 0.297 + 6 155 vaccine I 3.659 0.473 + 3 156 vaccineI 3.563 0.212 + 1 7029 vaccine I 0.460 0.080 − 42 3512 vaccine II 0.2850.109 − 10 3514 vaccine II 1.764 0.596 + 8 3515 vaccine II 0.663 0.239 +8 3519 vaccine II 1.349 0.389 + 14 3522 vaccine II 0.575 0.178 − 11 3528vaccine II 0.660 0.257 + 11 3530 vaccine II 0.922 0.205 + 13 3531vaccine II 0.404 0.101 − 11 3532 vaccine II 0.708 0.294 + 8 3535 vaccineII 1.574 0.584 + 16 3537 vaccine II 2.761 0.338 + 9 3542 vaccine II0.407 0.173 − 17 7086 control I 0.271 0.036 − 24 7090 control I 0.2070.015 − 19 7113 control I 0.296 0.070 − 19 7115 control I 0.327 0.209 −15 7122 control I 0.259 0.055 − 22 7123 control I 0.258 0.039 − 16 7124control I 0.215 0.016 − 18 7131 control I 0.807 0.118 + 16 7132 controlI 0.290 0.102 − 27 7133 control I 0.259 0.042 − 14 2110 control II 0.3770.287 − 26 2112 control II 0.396 0.125 − 33 2116 control II 0.185 0.076− 37 2119 control II 0.295 0.116 − 42 AIY2 negative 0.208 0.036 − AIW5negative 0.271 0.128 − AIY3 negative 0.402 0.031 − AIU5 negative 0.1920.008 − AIY1 negative 0.222 0.024 − AIW7 negative 0.310 0.021 − AIY2negative 0.240 0.038 − AIU4 negative 0.402 0.158 − AIW6 negative 0.1990.049 − AIV1 negative 0.374 0.056 − AIW1 negative 0.233 0.045 − AIW3negative 0.283 0.045 − AIU3 negative 0.175 0.046 − AIW4 negative 0.1640.057 − AIW2 negative 0.323 0.070 − Neg. Ave 0.266 Neg. SD 0.040 Ave +2SD 0.346

[0116] TABLE 6 Correlation between development of neutropenia after FPVchallenge and anti-FPV antibodies measured by ELISA using recombinantantigen PFPVpVP2₄₇₇ Sample Group OD Ave. OD SD ELISA Panleuk? 79 vaccineI 3.952 0.294 + no 80 vaccine I 0.748 0.099 + no 100 vaccine I 1.6250.324 + no 116 vaccine I 2.915 0.373 + no 118 vaccine I 3.432 0.374 + no119 vaccine I 2.820 0.428 + no 122 vaccine I 2.174 0.278 + no 123vaccine I 2.780 0.410 + no 130 vaccine I 0.678 0.194 + no 148 vaccine I0.300 0.073 − no 155 vaccine I 1.550 0.247 + no 156 vaccine I 0.8080.206 + no 7029 vaccine I 1.041 0.136 + no 3512 vaccine II 0.505 0.122 −no 3514 vaccine II 0.450 0.074 − no 3515 vaccine II 0.547 0.115 − no3519 vaccine II 1.675 0.214 + no 3522 vaccine II 0.292 0.042 − no 3528vaccine II 0.395 0.091 − no 3530 vaccine II 0.369 0.102 − no 3531vaccine II 0.534 0.155 − no 3532 vaccine II 0.427 0.145 − no 3535vaccine II 0.345 0.078 − no 3537 vaccine II 1.221 0.353 + no 3542vaccine II 0.377 0.061 − no 7132 control I 1.115 0.297 + yes 7086control I 0.301 0.063 − yes 7090 control I 0.262 0.012 − yes 7113control I 0.275 0.065 − yes 7115 control I 0.596 0.157 − yes 7122control I 0.278 0.087 − yes 7123 control I 0.378 0.213 − yes 7124control I 0.615 0.308 +/− yes 7131 control I 0.377 0.083 − yes 7133control I 0.310 0.114 − yes 2110 control II 0.299 0.071 − yes 2112control II 0.578 0.199 − yes 2116 control II 0.324 0.125 − yes 2119control II 0.306 0.079 − yes AIY2 negative 0.236 0.042 − AIW5 negative0.145 0.093 − AIY3 negative 0.240 0.071 − AIU5 negative 0.153 0.055 −AIY1 negative 0.266 0.081 − AIW7 negative 0.195 0.092 − AIY2 negative0.214 0.138 − AIU4 negative 0.196 0.111 − AIW6 negative 0.162 0.043 −AIV1 negative 0.292 0.074 − AIW1 negative 0.228 0.068 − AIW3 negative0.121 0.030 − AIU3 negative 0.122 0.037 − AIW4 negative 0.165 0.053 −AIW2 negative 0.209 0.066 − Neg. Ave 0.196 Neg. SD 0.030 Ave + 2SD 0.256

[0117] These data indicate the utility of an immune status of thepresent invention in predicting that a cat is protected from viralchallenge. Specifically, the results in Table 4 indicate that all 26vaccinated cats were protected from FCV challenge and that each of thosecats had antibody levels predicting protection. The results in Table 5indicate that 22 of 26 vaccinated cats were protected from FHV-1challenge and that 18 of the 22 protected cats had antibody levelspredicting protection. Of the four cats in this group that were notprotected, 2 cats had antibody levels predicting lack of protection and2 cats had antibody levels predicting protection. The results in Table 6indicate that neutropenia was detected in all 14 unvaccinated cats butin none of the vaccinated cats, confirming panleukopenia in theunvaccinated cats. Of the vaccinated cats, 14 of the 25 cats availablefor study had FPV antibody levels predicting protection.

[0118] In conclusion, an immune status assay of the present inventionshows high positive correlation with protection from challenge inhealthy, vaccinated cats exposed to virulent FCV, FHV-1, or FPV.

[0119] While various embodiments of the present invention have beendescribed in detail, it is apparent that modifications and adaptationsof those embodiments will occur to those skilled in the art. It is to beexpressly understood, however, that such modifications and adaptationsare within the scope of the present invention, as set forth in thefollowing claims.

1 36 1 2013 DNA Feline calicivirus CDS (1)..(2013) 1 atg tgc tca acc tgcgct aac gtg ctt aaa tat tat gat tgg gac ccc 48 Met Cys Ser Thr Cys AlaAsn Val Leu Lys Tyr Tyr Asp Trp Asp Pro 1 5 10 15 cat ttc aaa ttg gtaatc aac ccc aac aac ttc ctc tct gtt ggc ttt 96 His Phe Lys Leu Val IleAsn Pro Asn Asn Phe Leu Ser Val Gly Phe 20 25 30 tgt agt aac cct tta atgtgt tgc tac cca gaa ctc ctt ccg gaa ttt 144 Cys Ser Asn Pro Leu Met CysCys Tyr Pro Glu Leu Leu Pro Glu Phe 35 40 45 gga act gtt tgg gat tgc gatcgg tca cca ctt gaa att tac cta gaa 192 Gly Thr Val Trp Asp Cys Asp ArgSer Pro Leu Glu Ile Tyr Leu Glu 50 55 60 tca ata ctt ggt gat gat gaa tgggca tcc act ttt gac gct gtt gac 240 Ser Ile Leu Gly Asp Asp Glu Trp AlaSer Thr Phe Asp Ala Val Asp 65 70 75 80 cca gtc gtt ccc cca atg cac tggggt gct gct gga aaa att ttc cag 288 Pro Val Val Pro Pro Met His Trp GlyAla Ala Gly Lys Ile Phe Gln 85 90 95 cca cac ccc ggt gtt ctc atg cac catctc att ggt aag gtt gct gca 336 Pro His Pro Gly Val Leu Met His His LeuIle Gly Lys Val Ala Ala 100 105 110 ggt tgg gac ccc gat ctg cct cta attcga ctc gag gcg gat gac ggg 384 Gly Trp Asp Pro Asp Leu Pro Leu Ile ArgLeu Glu Ala Asp Asp Gly 115 120 125 tca atc aca gca ccc gag caa gga acaatg gtt ggc ggc gtc atc gct 432 Ser Ile Thr Ala Pro Glu Gln Gly Thr MetVal Gly Gly Val Ile Ala 130 135 140 gaa ccc agc gcc cag atg tca aca gctgct gat atg gcc acc ggg aaa 480 Glu Pro Ser Ala Gln Met Ser Thr Ala AlaAsp Met Ala Thr Gly Lys 145 150 155 160 agc gtt gat tct gag tgg gag gcattc ttc tcc ttt cac acc agc gtc 528 Ser Val Asp Ser Glu Trp Glu Ala PhePhe Ser Phe His Thr Ser Val 165 170 175 aat tgg agt aca tct gaa acc caagga aag att ctc ttc aaa caa tcc 576 Asn Trp Ser Thr Ser Glu Thr Gln GlyLys Ile Leu Phe Lys Gln Ser 180 185 190 tta ggc cct ttg ctc aac cca tatcta gaa cac ctt gct aag cta tat 624 Leu Gly Pro Leu Leu Asn Pro Tyr LeuGlu His Leu Ala Lys Leu Tyr 195 200 205 gtt gcg tgg tct ggg tcg att gaggtt agg ttc tct atc tct ggc tct 672 Val Ala Trp Ser Gly Ser Ile Glu ValArg Phe Ser Ile Ser Gly Ser 210 215 220 ggt gtc ttt ggt ggg aag ctc gcagct att gtt gta cct cct ggg gtt 720 Gly Val Phe Gly Gly Lys Leu Ala AlaIle Val Val Pro Pro Gly Val 225 230 235 240 gat cca gtg cag agt act tcgatg cta caa tac ccc cat gtt ttg ttt 768 Asp Pro Val Gln Ser Thr Ser MetLeu Gln Tyr Pro His Val Leu Phe 245 250 255 gat gct cgt cag gtg gaa ccagtt atc ttc tgt ctt cct gat cta aga 816 Asp Ala Arg Gln Val Glu Pro ValIle Phe Cys Leu Pro Asp Leu Arg 260 265 270 agc acc ctg tac cac ctt atgtct gac act gac act aca tcc ttg gtc 864 Ser Thr Leu Tyr His Leu Met SerAsp Thr Asp Thr Thr Ser Leu Val 275 280 285 att atg gtg tac aat gat ctcatc aat ccc tat gcc aat gat gcc aac 912 Ile Met Val Tyr Asn Asp Leu IleAsn Pro Tyr Ala Asn Asp Ala Asn 290 295 300 tct tct ggg tgt att gtc actgtc gag aca aaa cct ggc cct gac ttc 960 Ser Ser Gly Cys Ile Val Thr ValGlu Thr Lys Pro Gly Pro Asp Phe 305 310 315 320 aag ttt cac ctc ctt aagcca ccc gga tct atg cta acc cat ggc tct 1008 Lys Phe His Leu Leu Lys ProPro Gly Ser Met Leu Thr His Gly Ser 325 330 335 atc cct tct gat tta attccc aaa aca tct tcg ctc tgg atc ggt aac 1056 Ile Pro Ser Asp Leu Ile ProLys Thr Ser Ser Leu Trp Ile Gly Asn 340 345 350 cgc tac tgg tca gac ataact gat ttt gtg att cgg ccg ttt gtc ttc 1104 Arg Tyr Trp Ser Asp Ile ThrAsp Phe Val Ile Arg Pro Phe Val Phe 355 360 365 caa gca aat cgt cat tttgac ttt aat caa gag acc gca ggg tgg agc 1152 Gln Ala Asn Arg His Phe AspPhe Asn Gln Glu Thr Ala Gly Trp Ser 370 375 380 aca cca cgg ttt cgg cctata tct gtt acc att act gaa cag aac gga 1200 Thr Pro Arg Phe Arg Pro IleSer Val Thr Ile Thr Glu Gln Asn Gly 385 390 395 400 gca aaa ttg ggc attggg gtg gca aca gat tac ata gtg cct gga atc 1248 Ala Lys Leu Gly Ile GlyVal Ala Thr Asp Tyr Ile Val Pro Gly Ile 405 410 415 cct gat ggc tgg cctgac acc aca att cct ggg gag ttg ata cca gct 1296 Pro Asp Gly Trp Pro AspThr Thr Ile Pro Gly Glu Leu Ile Pro Ala 420 425 430 ggt gat tac gca atcacc aat ggt act ggc aat gac atc acc acg gct 1344 Gly Asp Tyr Ala Ile ThrAsn Gly Thr Gly Asn Asp Ile Thr Thr Ala 435 440 445 aca gga tat gac actgct gat ata att aag aac aat acc aac ttt agg 1392 Thr Gly Tyr Asp Thr AlaAsp Ile Ile Lys Asn Asn Thr Asn Phe Arg 450 455 460 ggc atg tac ata tgtggt tcg ctc cag cgt gcc tgg ggt gat aag aaa 1440 Gly Met Tyr Ile Cys GlySer Leu Gln Arg Ala Trp Gly Asp Lys Lys 465 470 475 480 att tcc aac actgcc ttt atc acc act gcc acc cta gat ggt gac aac 1488 Ile Ser Asn Thr AlaPhe Ile Thr Thr Ala Thr Leu Asp Gly Asp Asn 485 490 495 aac aac aag atcaat ccc tgt aat acc ata gac cag tca aag atc gtc 1536 Asn Asn Lys Ile AsnPro Cys Asn Thr Ile Asp Gln Ser Lys Ile Val 500 505 510 gtg ttt caa gacaac cat gtt gga aag aaa gcg caa acc tca gac gat 1584 Val Phe Gln Asp AsnHis Val Gly Lys Lys Ala Gln Thr Ser Asp Asp 515 520 525 aca ttg gcc ctgctt ggt tac act ggc att ggt gag cag gcc atc ggg 1632 Thr Leu Ala Leu LeuGly Tyr Thr Gly Ile Gly Glu Gln Ala Ile Gly 530 535 540 tct gat agg gaccgg gtt gtg cgc atc agc act ctc cct gaa act ggt 1680 Ser Asp Arg Asp ArgVal Val Arg Ile Ser Thr Leu Pro Glu Thr Gly 545 550 555 560 gct cga ggcggt aac cac cca att ttc tac aag aac tcc att aaa ttg 1728 Ala Arg Gly GlyAsn His Pro Ile Phe Tyr Lys Asn Ser Ile Lys Leu 565 570 575 gga tat gtaatt agg tct att gat gtc ttt aat tca caa atc ttg cac 1776 Gly Tyr Val IleArg Ser Ile Asp Val Phe Asn Ser Gln Ile Leu His 580 585 590 act tcc agacag tta tcg cta aat cat tac cta ctc cca cct gat tct 1824 Thr Ser Arg GlnLeu Ser Leu Asn His Tyr Leu Leu Pro Pro Asp Ser 595 600 605 ttt gcc gtctat aga ata att gac tca aat ggc tcg tgg ttt gat att 1872 Phe Ala Val TyrArg Ile Ile Asp Ser Asn Gly Ser Trp Phe Asp Ile 610 615 620 gga att gatagt gat ggg ttc tct ttt gtt ggt gtt tct ggc ttt ggt 1920 Gly Ile Asp SerAsp Gly Phe Ser Phe Val Gly Val Ser Gly Phe Gly 625 630 635 640 aaa ttagaa ttt ccc ctt tct gcc tcc tac atg gga ata caa ttg gca 1968 Lys Leu GluPhe Pro Leu Ser Ala Ser Tyr Met Gly Ile Gln Leu Ala 645 650 655 aag atccgg ctt gcc tct aac att agg agt ccc atg act aag tta 2013 Lys Ile Arg LeuAla Ser Asn Ile Arg Ser Pro Met Thr Lys Leu 660 665 670 2 671 PRT Felinecalicivirus 2 Met Cys Ser Thr Cys Ala Asn Val Leu Lys Tyr Tyr Asp TrpAsp Pro 1 5 10 15 His Phe Lys Leu Val Ile Asn Pro Asn Asn Phe Leu SerVal Gly Phe 20 25 30 Cys Ser Asn Pro Leu Met Cys Cys Tyr Pro Glu Leu LeuPro Glu Phe 35 40 45 Gly Thr Val Trp Asp Cys Asp Arg Ser Pro Leu Glu IleTyr Leu Glu 50 55 60 Ser Ile Leu Gly Asp Asp Glu Trp Ala Ser Thr Phe AspAla Val Asp 65 70 75 80 Pro Val Val Pro Pro Met His Trp Gly Ala Ala GlyLys Ile Phe Gln 85 90 95 Pro His Pro Gly Val Leu Met His His Leu Ile GlyLys Val Ala Ala 100 105 110 Gly Trp Asp Pro Asp Leu Pro Leu Ile Arg LeuGlu Ala Asp Asp Gly 115 120 125 Ser Ile Thr Ala Pro Glu Gln Gly Thr MetVal Gly Gly Val Ile Ala 130 135 140 Glu Pro Ser Ala Gln Met Ser Thr AlaAla Asp Met Ala Thr Gly Lys 145 150 155 160 Ser Val Asp Ser Glu Trp GluAla Phe Phe Ser Phe His Thr Ser Val 165 170 175 Asn Trp Ser Thr Ser GluThr Gln Gly Lys Ile Leu Phe Lys Gln Ser 180 185 190 Leu Gly Pro Leu LeuAsn Pro Tyr Leu Glu His Leu Ala Lys Leu Tyr 195 200 205 Val Ala Trp SerGly Ser Ile Glu Val Arg Phe Ser Ile Ser Gly Ser 210 215 220 Gly Val PheGly Gly Lys Leu Ala Ala Ile Val Val Pro Pro Gly Val 225 230 235 240 AspPro Val Gln Ser Thr Ser Met Leu Gln Tyr Pro His Val Leu Phe 245 250 255Asp Ala Arg Gln Val Glu Pro Val Ile Phe Cys Leu Pro Asp Leu Arg 260 265270 Ser Thr Leu Tyr His Leu Met Ser Asp Thr Asp Thr Thr Ser Leu Val 275280 285 Ile Met Val Tyr Asn Asp Leu Ile Asn Pro Tyr Ala Asn Asp Ala Asn290 295 300 Ser Ser Gly Cys Ile Val Thr Val Glu Thr Lys Pro Gly Pro AspPhe 305 310 315 320 Lys Phe His Leu Leu Lys Pro Pro Gly Ser Met Leu ThrHis Gly Ser 325 330 335 Ile Pro Ser Asp Leu Ile Pro Lys Thr Ser Ser LeuTrp Ile Gly Asn 340 345 350 Arg Tyr Trp Ser Asp Ile Thr Asp Phe Val IleArg Pro Phe Val Phe 355 360 365 Gln Ala Asn Arg His Phe Asp Phe Asn GlnGlu Thr Ala Gly Trp Ser 370 375 380 Thr Pro Arg Phe Arg Pro Ile Ser ValThr Ile Thr Glu Gln Asn Gly 385 390 395 400 Ala Lys Leu Gly Ile Gly ValAla Thr Asp Tyr Ile Val Pro Gly Ile 405 410 415 Pro Asp Gly Trp Pro AspThr Thr Ile Pro Gly Glu Leu Ile Pro Ala 420 425 430 Gly Asp Tyr Ala IleThr Asn Gly Thr Gly Asn Asp Ile Thr Thr Ala 435 440 445 Thr Gly Tyr AspThr Ala Asp Ile Ile Lys Asn Asn Thr Asn Phe Arg 450 455 460 Gly Met TyrIle Cys Gly Ser Leu Gln Arg Ala Trp Gly Asp Lys Lys 465 470 475 480 IleSer Asn Thr Ala Phe Ile Thr Thr Ala Thr Leu Asp Gly Asp Asn 485 490 495Asn Asn Lys Ile Asn Pro Cys Asn Thr Ile Asp Gln Ser Lys Ile Val 500 505510 Val Phe Gln Asp Asn His Val Gly Lys Lys Ala Gln Thr Ser Asp Asp 515520 525 Thr Leu Ala Leu Leu Gly Tyr Thr Gly Ile Gly Glu Gln Ala Ile Gly530 535 540 Ser Asp Arg Asp Arg Val Val Arg Ile Ser Thr Leu Pro Glu ThrGly 545 550 555 560 Ala Arg Gly Gly Asn His Pro Ile Phe Tyr Lys Asn SerIle Lys Leu 565 570 575 Gly Tyr Val Ile Arg Ser Ile Asp Val Phe Asn SerGln Ile Leu His 580 585 590 Thr Ser Arg Gln Leu Ser Leu Asn His Tyr LeuLeu Pro Pro Asp Ser 595 600 605 Phe Ala Val Tyr Arg Ile Ile Asp Ser AsnGly Ser Trp Phe Asp Ile 610 615 620 Gly Ile Asp Ser Asp Gly Phe Ser PheVal Gly Val Ser Gly Phe Gly 625 630 635 640 Lys Leu Glu Phe Pro Leu SerAla Ser Tyr Met Gly Ile Gln Leu Ala 645 650 655 Lys Ile Arg Leu Ala SerAsn Ile Arg Ser Pro Met Thr Lys Leu 660 665 670 3 1641 DNA Felinecalicivirus CDS (1)..(1641) 3 gcg gat gac ggg tca atc aca gca ccc gagcaa gga aca atg gtt ggc 48 Ala Asp Asp Gly Ser Ile Thr Ala Pro Glu GlnGly Thr Met Val Gly 1 5 10 15 ggc gtc atc gct gaa ccc agc gcc cag atgtca aca gct gct gat atg 96 Gly Val Ile Ala Glu Pro Ser Ala Gln Met SerThr Ala Ala Asp Met 20 25 30 gcc acc ggg aaa agc gtt gat tct gag tgg gaggca ttc ttc tcc ttt 144 Ala Thr Gly Lys Ser Val Asp Ser Glu Trp Glu AlaPhe Phe Ser Phe 35 40 45 cac acc agc gtc aat tgg agt aca tct gaa acc caagga aag att ctc 192 His Thr Ser Val Asn Trp Ser Thr Ser Glu Thr Gln GlyLys Ile Leu 50 55 60 ttc aaa caa tcc tta ggc cct ttg ctc aac cca tat ctagaa cac ctt 240 Phe Lys Gln Ser Leu Gly Pro Leu Leu Asn Pro Tyr Leu GluHis Leu 65 70 75 80 gct aag cta tat gtt gcg tgg tct ggg tcg att gag gttagg ttc tct 288 Ala Lys Leu Tyr Val Ala Trp Ser Gly Ser Ile Glu Val ArgPhe Ser 85 90 95 atc tct ggc tct ggt gtc ttt ggt ggg aag ctc gca gct attgtt gta 336 Ile Ser Gly Ser Gly Val Phe Gly Gly Lys Leu Ala Ala Ile ValVal 100 105 110 cct cct ggg gtt gat cca gtg cag agt act tcg atg cta caatac ccc 384 Pro Pro Gly Val Asp Pro Val Gln Ser Thr Ser Met Leu Gln TyrPro 115 120 125 cat gtt ttg ttt gat gct cgt cag gtg gaa cca gtt atc ttctgt ctt 432 His Val Leu Phe Asp Ala Arg Gln Val Glu Pro Val Ile Phe CysLeu 130 135 140 cct gat cta aga agc acc ctg tac cac ctt atg tct gac actgac act 480 Pro Asp Leu Arg Ser Thr Leu Tyr His Leu Met Ser Asp Thr AspThr 145 150 155 160 aca tcc ttg gtc att atg gtg tac aat gat ctc atc aatccc tat gcc 528 Thr Ser Leu Val Ile Met Val Tyr Asn Asp Leu Ile Asn ProTyr Ala 165 170 175 aat gat gcc aac tct tct ggg tgt att gtc act gtc gagaca aaa cct 576 Asn Asp Ala Asn Ser Ser Gly Cys Ile Val Thr Val Glu ThrLys Pro 180 185 190 ggc cct gac ttc aag ttt cac ctc ctt aag cca ccc ggatct atg cta 624 Gly Pro Asp Phe Lys Phe His Leu Leu Lys Pro Pro Gly SerMet Leu 195 200 205 acc cat ggc tct atc cct tct gat tta att ccc aaa acatct tcg ctc 672 Thr His Gly Ser Ile Pro Ser Asp Leu Ile Pro Lys Thr SerSer Leu 210 215 220 tgg atc ggt aac cgc tac tgg tca gac ata act gat tttgtg att cgg 720 Trp Ile Gly Asn Arg Tyr Trp Ser Asp Ile Thr Asp Phe ValIle Arg 225 230 235 240 ccg ttt gtc ttc caa gca aat cgt cat ttt gac tttaat caa gag acc 768 Pro Phe Val Phe Gln Ala Asn Arg His Phe Asp Phe AsnGln Glu Thr 245 250 255 gca ggg tgg agc aca cca cgg ttt cgg cct ata tctgtt acc att act 816 Ala Gly Trp Ser Thr Pro Arg Phe Arg Pro Ile Ser ValThr Ile Thr 260 265 270 gaa cag aac gga gca aaa ttg ggc att ggg gtg gcaaca gat tac ata 864 Glu Gln Asn Gly Ala Lys Leu Gly Ile Gly Val Ala ThrAsp Tyr Ile 275 280 285 gtg cct gga atc cct gat ggc tgg cct gac acc acaatt cct ggg gag 912 Val Pro Gly Ile Pro Asp Gly Trp Pro Asp Thr Thr IlePro Gly Glu 290 295 300 ttg ata cca gct ggt gat tac gca atc acc aat ggtact ggc aat gac 960 Leu Ile Pro Ala Gly Asp Tyr Ala Ile Thr Asn Gly ThrGly Asn Asp 305 310 315 320 atc acc acg gct aca gga tat gac act gct gatata att aag aac aat 1008 Ile Thr Thr Ala Thr Gly Tyr Asp Thr Ala Asp IleIle Lys Asn Asn 325 330 335 acc aac ttt agg ggc atg tac ata tgt ggt tcgctc cag cgt gcc tgg 1056 Thr Asn Phe Arg Gly Met Tyr Ile Cys Gly Ser LeuGln Arg Ala Trp 340 345 350 ggt gat aag aaa att tcc aac act gcc ttt atcacc act gcc acc cta 1104 Gly Asp Lys Lys Ile Ser Asn Thr Ala Phe Ile ThrThr Ala Thr Leu 355 360 365 gat ggt gac aac aac aac aag atc aat ccc tgtaat acc ata gac cag 1152 Asp Gly Asp Asn Asn Asn Lys Ile Asn Pro Cys AsnThr Ile Asp Gln 370 375 380 tca aag atc gtc gtg ttt caa gac aac cat gttgga aag aaa gcg caa 1200 Ser Lys Ile Val Val Phe Gln Asp Asn His Val GlyLys Lys Ala Gln 385 390 395 400 acc tca gac gat aca ttg gcc ctg ctt ggttac act ggc att ggt gag 1248 Thr Ser Asp Asp Thr Leu Ala Leu Leu Gly TyrThr Gly Ile Gly Glu 405 410 415 cag gcc atc ggg tct gat agg gac cgg gttgtg cgc atc agc act ctc 1296 Gln Ala Ile Gly Ser Asp Arg Asp Arg Val ValArg Ile Ser Thr Leu 420 425 430 cct gaa act ggt gct cga ggc ggt aac caccca att ttc tac aag aac 1344 Pro Glu Thr Gly Ala Arg Gly Gly Asn His ProIle Phe Tyr Lys Asn 435 440 445 tcc att aaa ttg gga tat gta att agg tctatt gat gtc ttt aat tca 1392 Ser Ile Lys Leu Gly Tyr Val Ile Arg Ser IleAsp Val Phe Asn Ser 450 455 460 caa atc ttg cac act tcc aga cag tta tcgcta aat cat tac cta ctc 1440 Gln Ile Leu His Thr Ser Arg Gln Leu Ser LeuAsn His Tyr Leu Leu 465 470 475 480 cca cct gat tct ttt gcc gtc tat agaata att gac tca aat ggc tcg 1488 Pro Pro Asp Ser Phe Ala Val Tyr Arg IleIle Asp Ser Asn Gly Ser 485 490 495 tgg ttt gat att gga att gat agt gatggg ttc tct ttt gtt ggt gtt 1536 Trp Phe Asp Ile Gly Ile Asp Ser Asp GlyPhe Ser Phe Val Gly Val 500 505 510 tct ggc ttt ggt aaa tta gaa ttt cccctt tct gcc tcc tac atg gga 1584 Ser Gly Phe Gly Lys Leu Glu Phe Pro LeuSer Ala Ser Tyr Met Gly 515 520 525 ata caa ttg gca aag atc cgg ctt gcctct aac att agg agt ccc atg 1632 Ile Gln Leu Ala Lys Ile Arg Leu Ala SerAsn Ile Arg Ser Pro Met 530 535 540 act aag tta 1641 Thr Lys Leu 545 4547 PRT Feline calicivirus 4 Ala Asp Asp Gly Ser Ile Thr Ala Pro Glu GlnGly Thr Met Val Gly 1 5 10 15 Gly Val Ile Ala Glu Pro Ser Ala Gln MetSer Thr Ala Ala Asp Met 20 25 30 Ala Thr Gly Lys Ser Val Asp Ser Glu TrpGlu Ala Phe Phe Ser Phe 35 40 45 His Thr Ser Val Asn Trp Ser Thr Ser GluThr Gln Gly Lys Ile Leu 50 55 60 Phe Lys Gln Ser Leu Gly Pro Leu Leu AsnPro Tyr Leu Glu His Leu 65 70 75 80 Ala Lys Leu Tyr Val Ala Trp Ser GlySer Ile Glu Val Arg Phe Ser 85 90 95 Ile Ser Gly Ser Gly Val Phe Gly GlyLys Leu Ala Ala Ile Val Val 100 105 110 Pro Pro Gly Val Asp Pro Val GlnSer Thr Ser Met Leu Gln Tyr Pro 115 120 125 His Val Leu Phe Asp Ala ArgGln Val Glu Pro Val Ile Phe Cys Leu 130 135 140 Pro Asp Leu Arg Ser ThrLeu Tyr His Leu Met Ser Asp Thr Asp Thr 145 150 155 160 Thr Ser Leu ValIle Met Val Tyr Asn Asp Leu Ile Asn Pro Tyr Ala 165 170 175 Asn Asp AlaAsn Ser Ser Gly Cys Ile Val Thr Val Glu Thr Lys Pro 180 185 190 Gly ProAsp Phe Lys Phe His Leu Leu Lys Pro Pro Gly Ser Met Leu 195 200 205 ThrHis Gly Ser Ile Pro Ser Asp Leu Ile Pro Lys Thr Ser Ser Leu 210 215 220Trp Ile Gly Asn Arg Tyr Trp Ser Asp Ile Thr Asp Phe Val Ile Arg 225 230235 240 Pro Phe Val Phe Gln Ala Asn Arg His Phe Asp Phe Asn Gln Glu Thr245 250 255 Ala Gly Trp Ser Thr Pro Arg Phe Arg Pro Ile Ser Val Thr IleThr 260 265 270 Glu Gln Asn Gly Ala Lys Leu Gly Ile Gly Val Ala Thr AspTyr Ile 275 280 285 Val Pro Gly Ile Pro Asp Gly Trp Pro Asp Thr Thr IlePro Gly Glu 290 295 300 Leu Ile Pro Ala Gly Asp Tyr Ala Ile Thr Asn GlyThr Gly Asn Asp 305 310 315 320 Ile Thr Thr Ala Thr Gly Tyr Asp Thr AlaAsp Ile Ile Lys Asn Asn 325 330 335 Thr Asn Phe Arg Gly Met Tyr Ile CysGly Ser Leu Gln Arg Ala Trp 340 345 350 Gly Asp Lys Lys Ile Ser Asn ThrAla Phe Ile Thr Thr Ala Thr Leu 355 360 365 Asp Gly Asp Asn Asn Asn LysIle Asn Pro Cys Asn Thr Ile Asp Gln 370 375 380 Ser Lys Ile Val Val PheGln Asp Asn His Val Gly Lys Lys Ala Gln 385 390 395 400 Thr Ser Asp AspThr Leu Ala Leu Leu Gly Tyr Thr Gly Ile Gly Glu 405 410 415 Gln Ala IleGly Ser Asp Arg Asp Arg Val Val Arg Ile Ser Thr Leu 420 425 430 Pro GluThr Gly Ala Arg Gly Gly Asn His Pro Ile Phe Tyr Lys Asn 435 440 445 SerIle Lys Leu Gly Tyr Val Ile Arg Ser Ile Asp Val Phe Asn Ser 450 455 460Gln Ile Leu His Thr Ser Arg Gln Leu Ser Leu Asn His Tyr Leu Leu 465 470475 480 Pro Pro Asp Ser Phe Ala Val Tyr Arg Ile Ile Asp Ser Asn Gly Ser485 490 495 Trp Phe Asp Ile Gly Ile Asp Ser Asp Gly Phe Ser Phe Val GlyVal 500 505 510 Ser Gly Phe Gly Lys Leu Glu Phe Pro Leu Ser Ala Ser TyrMet Gly 515 520 525 Ile Gln Leu Ala Lys Ile Arg Leu Ala Ser Asn Ile ArgSer Pro Met 530 535 540 Thr Lys Leu 545 5 1752 DNA Feline parvovirus CDS(1)..(1752) 5 atg agt gat gga gca gtt caa cca gac ggt ggt caa cct gctgtc aga 48 Met Ser Asp Gly Ala Val Gln Pro Asp Gly Gly Gln Pro Ala ValArg 1 5 10 15 aat gaa aga gct aca gga tct ggg aac ggg tct gga ggc gggggt ggt 96 Asn Glu Arg Ala Thr Gly Ser Gly Asn Gly Ser Gly Gly Gly GlyGly 20 25 30 ggt ggt tct ggg ggt gtg ggg att tct acg ggt act ttc aat aatcag 144 Gly Gly Ser Gly Gly Val Gly Ile Ser Thr Gly Thr Phe Asn Asn Gln35 40 45 acg gaa ttt aaa ttt ttg gaa aac ggg tgg gtg gaa atc aca gca aac192 Thr Glu Phe Lys Phe Leu Glu Asn Gly Trp Val Glu Ile Thr Ala Asn 5055 60 tca agc aga ctt gta cat tta aat atg cca gaa agt gaa aat tat aaa240 Ser Ser Arg Leu Val His Leu Asn Met Pro Glu Ser Glu Asn Tyr Lys 6570 75 80 aga gta gtt gta aat aat atg gat aaa act gca gtt aaa gga aac atg288 Arg Val Val Val Asn Asn Met Asp Lys Thr Ala Val Lys Gly Asn Met 8590 95 gct tta gat gat att cat gta caa att gta aca cct tgg tca ttg gtt336 Ala Leu Asp Asp Ile His Val Gln Ile Val Thr Pro Trp Ser Leu Val 100105 110 gat gca aat gct tgg gga gtt tgg ttt aat cca gga gat tgg caa cta384 Asp Ala Asn Ala Trp Gly Val Trp Phe Asn Pro Gly Asp Trp Gln Leu 115120 125 att gtt aat act atg agt gag ttg cat tta gtt agt ttt gaa caa gaa432 Ile Val Asn Thr Met Ser Glu Leu His Leu Val Ser Phe Glu Gln Glu 130135 140 att ttt aat gtt gtt tta aag act gtt tca gaa tct gct act cag cca480 Ile Phe Asn Val Val Leu Lys Thr Val Ser Glu Ser Ala Thr Gln Pro 145150 155 160 cca act aaa gtt tat aat aat gat tta act gca tca ttg atg gttgca 528 Pro Thr Lys Val Tyr Asn Asn Asp Leu Thr Ala Ser Leu Met Val Ala165 170 175 tta gat agt aat aat act atg cca ttt act cca gca gct atg agatct 576 Leu Asp Ser Asn Asn Thr Met Pro Phe Thr Pro Ala Ala Met Arg Ser180 185 190 gag aca ttg ggt ttt tat cca tgg aaa cca acc ata cca act ccatgg 624 Glu Thr Leu Gly Phe Tyr Pro Trp Lys Pro Thr Ile Pro Thr Pro Trp195 200 205 aga tat tat ttt caa tgg gat aga aca tta ata cca tct cat actgga 672 Arg Tyr Tyr Phe Gln Trp Asp Arg Thr Leu Ile Pro Ser His Thr Gly210 215 220 act agt ggc aca cca aca aat gta tat cat ggt aca gat cca gatgat 720 Thr Ser Gly Thr Pro Thr Asn Val Tyr His Gly Thr Asp Pro Asp Asp225 230 235 240 gtt caa ttt tat act att gaa aat tct gtg cca gta cac ttacta aga 768 Val Gln Phe Tyr Thr Ile Glu Asn Ser Val Pro Val His Leu LeuArg 245 250 255 aca ggt gat gaa ttt gct aca gga aca ttt ttt ttt gat tgtaaa cca 816 Thr Gly Asp Glu Phe Ala Thr Gly Thr Phe Phe Phe Asp Cys LysPro 260 265 270 tgt aga tta aca cat aca tgg caa aca aat aga gca ttg ggctta cca 864 Cys Arg Leu Thr His Thr Trp Gln Thr Asn Arg Ala Leu Gly LeuPro 275 280 285 cca ttt tta aat tct ttg cct caa tct gaa gga gct act aacttt ggt 912 Pro Phe Leu Asn Ser Leu Pro Gln Ser Glu Gly Ala Thr Asn PheGly 290 295 300 gat ata gga gtt caa caa gat aaa aga cgt ggt gta act caaatg gga 960 Asp Ile Gly Val Gln Gln Asp Lys Arg Arg Gly Val Thr Gln MetGly 305 310 315 320 aat aca gac tat att act gaa gct act att atg aga ccagct gag gtt 1008 Asn Thr Asp Tyr Ile Thr Glu Ala Thr Ile Met Arg Pro AlaGlu Val 325 330 335 ggt tat agt gca cca tat tat tct ttt gaa gcg tct acacaa ggg cca 1056 Gly Tyr Ser Ala Pro Tyr Tyr Ser Phe Glu Ala Ser Thr GlnGly Pro 340 345 350 ttt aaa aca cct att gca gca gga cgg ggg gga gcg caaaca gat gaa 1104 Phe Lys Thr Pro Ile Ala Ala Gly Arg Gly Gly Ala Gln ThrAsp Glu 355 360 365 aat caa gca gca gat ggt gat cca aga tat gca ttt ggtaga caa cat 1152 Asn Gln Ala Ala Asp Gly Asp Pro Arg Tyr Ala Phe Gly ArgGln His 370 375 380 ggt caa aaa act act aca aca gga gaa aca cct gag agattt aca tat 1200 Gly Gln Lys Thr Thr Thr Thr Gly Glu Thr Pro Glu Arg PheThr Tyr 385 390 395 400 ata gca cat caa gat aca gga aga tat cca gaa ggagat tgg att caa 1248 Ile Ala His Gln Asp Thr Gly Arg Tyr Pro Glu Gly AspTrp Ile Gln 405 410 415 aat att aac ttt aac ctt cct gta aca aat gat aatgta ttg cta cca 1296 Asn Ile Asn Phe Asn Leu Pro Val Thr Asn Asp Asn ValLeu Leu Pro 420 425 430 aca gat cca att ggg ggt aaa aca gga att aac tatact aat ata ttt 1344 Thr Asp Pro Ile Gly Gly Lys Thr Gly Ile Asn Tyr ThrAsn Ile Phe 435 440 445 aat act tat ggt cct tta act gca tta aat aat gtacca cca gtt tat 1392 Asn Thr Tyr Gly Pro Leu Thr Ala Leu Asn Asn Val ProPro Val Tyr 450 455 460 cca aat ggt caa att tgg gat aaa gaa ttt gat actgac tta aaa cca 1440 Pro Asn Gly Gln Ile Trp Asp Lys Glu Phe Asp Thr AspLeu Lys Pro 465 470 475 480 aga ctt cat gta aat gca cca ttt gtt tgt caaaat aat tgt cct ggt 1488 Arg Leu His Val Asn Ala Pro Phe Val Cys Gln AsnAsn Cys Pro Gly 485 490 495 caa tta ttt gta aaa gtt gcg cct aat tta acgaat gaa tat gat cct 1536 Gln Leu Phe Val Lys Val Ala Pro Asn Leu Thr AsnGlu Tyr Asp Pro 500 505 510 gat gca tct gct aat atg tca aga att gta acttat tca gat ttt tgg 1584 Asp Ala Ser Ala Asn Met Ser Arg Ile Val Thr TyrSer Asp Phe Trp 515 520 525 tgg aaa ggt aaa tta gta ttt aaa gct aaa ctaaga gca tct cat act 1632 Trp Lys Gly Lys Leu Val Phe Lys Ala Lys Leu ArgAla Ser His Thr 530 535 540 tgg aat cca att caa caa atg agc att aat gtagat aac caa ttt aac 1680 Trp Asn Pro Ile Gln Gln Met Ser Ile Asn Val AspAsn Gln Phe Asn 545 550 555 560 tat gta cca aat aat att gga gct atg aaaatt gta tat gaa aaa tct 1728 Tyr Val Pro Asn Asn Ile Gly Ala Met Lys IleVal Tyr Glu Lys Ser 565 570 575 caa cta gca cct aga aaa tta tat 1752 GlnLeu Ala Pro Arg Lys Leu Tyr 580 6 584 PRT Feline parvovirus 6 Met SerAsp Gly Ala Val Gln Pro Asp Gly Gly Gln Pro Ala Val Arg 1 5 10 15 AsnGlu Arg Ala Thr Gly Ser Gly Asn Gly Ser Gly Gly Gly Gly Gly 20 25 30 GlyGly Ser Gly Gly Val Gly Ile Ser Thr Gly Thr Phe Asn Asn Gln 35 40 45 ThrGlu Phe Lys Phe Leu Glu Asn Gly Trp Val Glu Ile Thr Ala Asn 50 55 60 SerSer Arg Leu Val His Leu Asn Met Pro Glu Ser Glu Asn Tyr Lys 65 70 75 80Arg Val Val Val Asn Asn Met Asp Lys Thr Ala Val Lys Gly Asn Met 85 90 95Ala Leu Asp Asp Ile His Val Gln Ile Val Thr Pro Trp Ser Leu Val 100 105110 Asp Ala Asn Ala Trp Gly Val Trp Phe Asn Pro Gly Asp Trp Gln Leu 115120 125 Ile Val Asn Thr Met Ser Glu Leu His Leu Val Ser Phe Glu Gln Glu130 135 140 Ile Phe Asn Val Val Leu Lys Thr Val Ser Glu Ser Ala Thr GlnPro 145 150 155 160 Pro Thr Lys Val Tyr Asn Asn Asp Leu Thr Ala Ser LeuMet Val Ala 165 170 175 Leu Asp Ser Asn Asn Thr Met Pro Phe Thr Pro AlaAla Met Arg Ser 180 185 190 Glu Thr Leu Gly Phe Tyr Pro Trp Lys Pro ThrIle Pro Thr Pro Trp 195 200 205 Arg Tyr Tyr Phe Gln Trp Asp Arg Thr LeuIle Pro Ser His Thr Gly 210 215 220 Thr Ser Gly Thr Pro Thr Asn Val TyrHis Gly Thr Asp Pro Asp Asp 225 230 235 240 Val Gln Phe Tyr Thr Ile GluAsn Ser Val Pro Val His Leu Leu Arg 245 250 255 Thr Gly Asp Glu Phe AlaThr Gly Thr Phe Phe Phe Asp Cys Lys Pro 260 265 270 Cys Arg Leu Thr HisThr Trp Gln Thr Asn Arg Ala Leu Gly Leu Pro 275 280 285 Pro Phe Leu AsnSer Leu Pro Gln Ser Glu Gly Ala Thr Asn Phe Gly 290 295 300 Asp Ile GlyVal Gln Gln Asp Lys Arg Arg Gly Val Thr Gln Met Gly 305 310 315 320 AsnThr Asp Tyr Ile Thr Glu Ala Thr Ile Met Arg Pro Ala Glu Val 325 330 335Gly Tyr Ser Ala Pro Tyr Tyr Ser Phe Glu Ala Ser Thr Gln Gly Pro 340 345350 Phe Lys Thr Pro Ile Ala Ala Gly Arg Gly Gly Ala Gln Thr Asp Glu 355360 365 Asn Gln Ala Ala Asp Gly Asp Pro Arg Tyr Ala Phe Gly Arg Gln His370 375 380 Gly Gln Lys Thr Thr Thr Thr Gly Glu Thr Pro Glu Arg Phe ThrTyr 385 390 395 400 Ile Ala His Gln Asp Thr Gly Arg Tyr Pro Glu Gly AspTrp Ile Gln 405 410 415 Asn Ile Asn Phe Asn Leu Pro Val Thr Asn Asp AsnVal Leu Leu Pro 420 425 430 Thr Asp Pro Ile Gly Gly Lys Thr Gly Ile AsnTyr Thr Asn Ile Phe 435 440 445 Asn Thr Tyr Gly Pro Leu Thr Ala Leu AsnAsn Val Pro Pro Val Tyr 450 455 460 Pro Asn Gly Gln Ile Trp Asp Lys GluPhe Asp Thr Asp Leu Lys Pro 465 470 475 480 Arg Leu His Val Asn Ala ProPhe Val Cys Gln Asn Asn Cys Pro Gly 485 490 495 Gln Leu Phe Val Lys ValAla Pro Asn Leu Thr Asn Glu Tyr Asp Pro 500 505 510 Asp Ala Ser Ala AsnMet Ser Arg Ile Val Thr Tyr Ser Asp Phe Trp 515 520 525 Trp Lys Gly LysLeu Val Phe Lys Ala Lys Leu Arg Ala Ser His Thr 530 535 540 Trp Asn ProIle Gln Gln Met Ser Ile Asn Val Asp Asn Gln Phe Asn 545 550 555 560 TyrVal Pro Asn Asn Ile Gly Ala Met Lys Ile Val Tyr Glu Lys Ser 565 570 575Gln Leu Ala Pro Arg Lys Leu Tyr 580 7 729 DNA Feline parvovirus CDS(1)..(729) 7 ggt aca gat cca gat gat gtt caa ttt tat act att gaa aat tctgtg 48 Gly Thr Asp Pro Asp Asp Val Gln Phe Tyr Thr Ile Glu Asn Ser Val 15 10 15 cca gta cac tta cta aga aca ggt gat gaa ttt gct aca gga aca ttt96 Pro Val His Leu Leu Arg Thr Gly Asp Glu Phe Ala Thr Gly Thr Phe 20 2530 ttt ttt gat tgt aaa cca tgt aga tta aca cat aca tgg caa aca aat 144Phe Phe Asp Cys Lys Pro Cys Arg Leu Thr His Thr Trp Gln Thr Asn 35 40 45aga gca ttg ggc tta cca cca ttt tta aat tct ttg cct caa tct gaa 192 ArgAla Leu Gly Leu Pro Pro Phe Leu Asn Ser Leu Pro Gln Ser Glu 50 55 60 ggagct act aac ttt ggt gat ata gga gtt caa caa gat aaa aga cgt 240 Gly AlaThr Asn Phe Gly Asp Ile Gly Val Gln Gln Asp Lys Arg Arg 65 70 75 80 ggtgta act caa atg gga aat aca gac tat att act gaa gct act att 288 Gly ValThr Gln Met Gly Asn Thr Asp Tyr Ile Thr Glu Ala Thr Ile 85 90 95 atg agacca gct gag gtt ggt tat agt gca cca tat tat tct ttt gaa 336 Met Arg ProAla Glu Val Gly Tyr Ser Ala Pro Tyr Tyr Ser Phe Glu 100 105 110 gcg tctaca caa ggg cca ttt aaa aca cct att gca gca gga cgg ggg 384 Ala Ser ThrGln Gly Pro Phe Lys Thr Pro Ile Ala Ala Gly Arg Gly 115 120 125 gga gcgcaa aca gat gaa aat caa gca gca gat ggt gat cca aga tat 432 Gly Ala GlnThr Asp Glu Asn Gln Ala Ala Asp Gly Asp Pro Arg Tyr 130 135 140 gca tttggt aga caa cat ggt caa aaa act act aca aca gga gaa aca 480 Ala Phe GlyArg Gln His Gly Gln Lys Thr Thr Thr Thr Gly Glu Thr 145 150 155 160 cctgag aga ttt aca tat ata gca cat caa gat aca gga aga tat cca 528 Pro GluArg Phe Thr Tyr Ile Ala His Gln Asp Thr Gly Arg Tyr Pro 165 170 175 gaagga gat tgg att caa aat att aac ttt aac ctt cct gta aca aat 576 Glu GlyAsp Trp Ile Gln Asn Ile Asn Phe Asn Leu Pro Val Thr Asn 180 185 190 gataat gta ttg cta cca aca gat cca att ggg ggt aaa aca gga att 624 Asp AsnVal Leu Leu Pro Thr Asp Pro Ile Gly Gly Lys Thr Gly Ile 195 200 205 aactat act aat ata ttt aat act tat ggt cct tta act gca tta aat 672 Asn TyrThr Asn Ile Phe Asn Thr Tyr Gly Pro Leu Thr Ala Leu Asn 210 215 220 aatgta cca cca gtt tat cca aat ggt caa att tgg gat aaa gaa ttt 720 Asn ValPro Pro Val Tyr Pro Asn Gly Gln Ile Trp Asp Lys Glu Phe 225 230 235 240gat act gac 729 Asp Thr Asp 8 243 PRT Feline parvovirus 8 Gly Thr AspPro Asp Asp Val Gln Phe Tyr Thr Ile Glu Asn Ser Val 1 5 10 15 Pro ValHis Leu Leu Arg Thr Gly Asp Glu Phe Ala Thr Gly Thr Phe 20 25 30 Phe PheAsp Cys Lys Pro Cys Arg Leu Thr His Thr Trp Gln Thr Asn 35 40 45 Arg AlaLeu Gly Leu Pro Pro Phe Leu Asn Ser Leu Pro Gln Ser Glu 50 55 60 Gly AlaThr Asn Phe Gly Asp Ile Gly Val Gln Gln Asp Lys Arg Arg 65 70 75 80 GlyVal Thr Gln Met Gly Asn Thr Asp Tyr Ile Thr Glu Ala Thr Ile 85 90 95 MetArg Pro Ala Glu Val Gly Tyr Ser Ala Pro Tyr Tyr Ser Phe Glu 100 105 110Ala Ser Thr Gln Gly Pro Phe Lys Thr Pro Ile Ala Ala Gly Arg Gly 115 120125 Gly Ala Gln Thr Asp Glu Asn Gln Ala Ala Asp Gly Asp Pro Arg Tyr 130135 140 Ala Phe Gly Arg Gln His Gly Gln Lys Thr Thr Thr Thr Gly Glu Thr145 150 155 160 Pro Glu Arg Phe Thr Tyr Ile Ala His Gln Asp Thr Gly ArgTyr Pro 165 170 175 Glu Gly Asp Trp Ile Gln Asn Ile Asn Phe Asn Leu ProVal Thr Asn 180 185 190 Asp Asn Val Leu Leu Pro Thr Asp Pro Ile Gly GlyLys Thr Gly Ile 195 200 205 Asn Tyr Thr Asn Ile Phe Asn Thr Tyr Gly ProLeu Thr Ala Leu Asn 210 215 220 Asn Val Pro Pro Val Tyr Pro Asn Gly GlnIle Trp Asp Lys Glu Phe 225 230 235 240 Asp Thr Asp 9 1860 DNA Felineparvovirus CDS (1)..(1860) 9 atg gca cct ccg gca aag aga gcc agg aga ggactt gtg cct cca ggt 48 Met Ala Pro Pro Ala Lys Arg Ala Arg Arg Gly LeuVal Pro Pro Gly 1 5 10 15 tat aaa tat ctt ggg cct ggg aac agt ctt gaccaa gga gaa cca act 96 Tyr Lys Tyr Leu Gly Pro Gly Asn Ser Leu Asp GlnGly Glu Pro Thr 20 25 30 aac cct tct gac gcc gct gca aaa gaa cac gac gaagct tac gct gct 144 Asn Pro Ser Asp Ala Ala Ala Lys Glu His Asp Glu AlaTyr Ala Ala 35 40 45 tat ctt cgc tct ggt aaa aac cca tac tta tat ttc tcgcca gca gat 192 Tyr Leu Arg Ser Gly Lys Asn Pro Tyr Leu Tyr Phe Ser ProAla Asp 50 55 60 caa cgc ttt ata gat caa act aag gac gct aca gat tgg gggggg aaa 240 Gln Arg Phe Ile Asp Gln Thr Lys Asp Ala Thr Asp Trp Gly GlyLys 65 70 75 80 ata gga cat tat ttt ttt aga gct aaa aaa gca att gct ccagta tta 288 Ile Gly His Tyr Phe Phe Arg Ala Lys Lys Ala Ile Ala Pro ValLeu 85 90 95 act gat aca cca gat cat cca tca aca tca aga cca aca aaa ccaact 336 Thr Asp Thr Pro Asp His Pro Ser Thr Ser Arg Pro Thr Lys Pro Thr100 105 110 aaa aga agt aaa cca cca cct cat att ttc atc aat ctt gca aaaaaa 384 Lys Arg Ser Lys Pro Pro Pro His Ile Phe Ile Asn Leu Ala Lys Lys115 120 125 aaa aaa gcc ggt gca gga caa gta aaa aga gac aat caa gca ccaatg 432 Lys Lys Ala Gly Ala Gly Gln Val Lys Arg Asp Asn Gln Ala Pro Met130 135 140 agt gat gga gca gtt caa cca gac ggt ggt caa cct gct gtc agaaat 480 Ser Asp Gly Ala Val Gln Pro Asp Gly Gly Gln Pro Ala Val Arg Asn145 150 155 160 gaa aga gct aca gga tct ggg aac ggg tct gga ggc ggg ggtggt ggt 528 Glu Arg Ala Thr Gly Ser Gly Asn Gly Ser Gly Gly Gly Gly GlyGly 165 170 175 ggt tct ggg ggt gtg ggg att tct acg ggt act ttc aat aatcag acg 576 Gly Ser Gly Gly Val Gly Ile Ser Thr Gly Thr Phe Asn Asn GlnThr 180 185 190 gaa ttt aaa ttt ttg gaa aac gga tgg gtg gaa atc aca gcaaac tca 624 Glu Phe Lys Phe Leu Glu Asn Gly Trp Val Glu Ile Thr Ala AsnSer 195 200 205 agc aga ctt gta cat tta aat atg cca gaa agt gaa aat tataaa aga 672 Ser Arg Leu Val His Leu Asn Met Pro Glu Ser Glu Asn Tyr LysArg 210 215 220 gta gtt gta aat aat atg gat aaa act gca gtt aaa gga aacatg gct 720 Val Val Val Asn Asn Met Asp Lys Thr Ala Val Lys Gly Asn MetAla 225 230 235 240 tta gat gac act cat gta caa att gta aca cct tgg tcattg gtt gat 768 Leu Asp Asp Thr His Val Gln Ile Val Thr Pro Trp Ser LeuVal Asp 245 250 255 gca aat gct tgg gga gtt tgg ttt aat cca gga gat tggcaa cta att 816 Ala Asn Ala Trp Gly Val Trp Phe Asn Pro Gly Asp Trp GlnLeu Ile 260 265 270 gtt aat act atg agt gag ttg cat tta gtt agt ttt gaacaa gaa att 864 Val Asn Thr Met Ser Glu Leu His Leu Val Ser Phe Glu GlnGlu Ile 275 280 285 ttt aat gtt gtt tta aag act gtt tca gaa tct gct actcag cca cca 912 Phe Asn Val Val Leu Lys Thr Val Ser Glu Ser Ala Thr GlnPro Pro 290 295 300 act aaa gtt tat aat aat gat tta act gca tca ttg atggtt gca tta 960 Thr Lys Val Tyr Asn Asn Asp Leu Thr Ala Ser Leu Met ValAla Leu 305 310 315 320 gat agt aat aat act atg cca ttt act cca gca gctatg aga tct gag 1008 Asp Ser Asn Asn Thr Met Pro Phe Thr Pro Ala Ala MetArg Ser Glu 325 330 335 aca ttg ggt ttt tat cca tgg aaa cca acc ata ccaact cca tgg aga 1056 Thr Leu Gly Phe Tyr Pro Trp Lys Pro Thr Ile Pro ThrPro Trp Arg 340 345 350 tat tat ttt caa tgg gat aga aca tta ata cca tctcat act gga act 1104 Tyr Tyr Phe Gln Trp Asp Arg Thr Leu Ile Pro Ser HisThr Gly Thr 355 360 365 agt ggc aca cca aca aat ata tat cat ggt aca gatcca gat gat gtt 1152 Ser Gly Thr Pro Thr Asn Ile Tyr His Gly Thr Asp ProAsp Asp Val 370 375 380 caa ttt tat act att gaa aat tct gtg cca gta cactta cta aga aca 1200 Gln Phe Tyr Thr Ile Glu Asn Ser Val Pro Val His LeuLeu Arg Thr 385 390 395 400 ggt gat gaa ttt gct aca gga aca ttt ttt tttgat tgt aaa cca tgt 1248 Gly Asp Glu Phe Ala Thr Gly Thr Phe Phe Phe AspCys Lys Pro Cys 405 410 415 aga cta aca cat aca tgg caa aca aac aga gcattg ggc tta cca cca 1296 Arg Leu Thr His Thr Trp Gln Thr Asn Arg Ala LeuGly Leu Pro Pro 420 425 430 ttt cta aat tct ttg cct caa tct gaa gga gctact aac ttt ggt gat 1344 Phe Leu Asn Ser Leu Pro Gln Ser Glu Gly Ala ThrAsn Phe Gly Asp 435 440 445 ata gga gtt caa caa gat aaa aga cgt ggt gtaact caa atg gga aat 1392 Ile Gly Val Gln Gln Asp Lys Arg Arg Gly Val ThrGln Met Gly Asn 450 455 460 aca gac tat att act gaa gct act att atg agacca gct gag gtt ggt 1440 Thr Asp Tyr Ile Thr Glu Ala Thr Ile Met Arg ProAla Glu Val Gly 465 470 475 480 tat agt gca cca tat tat tct ttt gaa gcgtct aca caa ggg cca ttt 1488 Tyr Ser Ala Pro Tyr Tyr Ser Phe Glu Ala SerThr Gln Gly Pro Phe 485 490 495 aaa ata cct att gca gca gga cgg ggg ggagcg caa aca gat gaa aat 1536 Lys Ile Pro Ile Ala Ala Gly Arg Gly Gly AlaGln Thr Asp Glu Asn 500 505 510 caa gca gca gat ggt gat cca aga tat gcattt ggt aga caa cat ggt 1584 Gln Ala Ala Asp Gly Asp Pro Arg Tyr Ala PheGly Arg Gln His Gly 515 520 525 caa aaa act act aca aca gga gaa aca cctgag aga ttt aca tat ata 1632 Gln Lys Thr Thr Thr Thr Gly Glu Thr Pro GluArg Phe Thr Tyr Ile 530 535 540 gca cat caa gat aca gga aga tat cca gcagga gat tgg att caa aat 1680 Ala His Gln Asp Thr Gly Arg Tyr Pro Ala GlyAsp Trp Ile Gln Asn 545 550 555 560 att aac ttt aac ctt cct gta aca aatgat aat gta ttg cta cca aca 1728 Ile Asn Phe Asn Leu Pro Val Thr Asn AspAsn Val Leu Leu Pro Thr 565 570 575 gat cca att gga ggt aaa aca gga atcaac tat act aat ata ttt aat 1776 Asp Pro Ile Gly Gly Lys Thr Gly Ile AsnTyr Thr Asn Ile Phe Asn 580 585 590 act tat ggt cct tta act gca tta aataat gta cca cca gtt tat cca 1824 Thr Tyr Gly Pro Leu Thr Ala Leu Asn AsnVal Pro Pro Val Tyr Pro 595 600 605 aat ggt caa att tgg gat aaa gaa tttgat act gac 1860 Asn Gly Gln Ile Trp Asp Lys Glu Phe Asp Thr Asp 610 615620 10 620 PRT Feline parvovirus 10 Met Ala Pro Pro Ala Lys Arg Ala ArgArg Gly Leu Val Pro Pro Gly 1 5 10 15 Tyr Lys Tyr Leu Gly Pro Gly AsnSer Leu Asp Gln Gly Glu Pro Thr 20 25 30 Asn Pro Ser Asp Ala Ala Ala LysGlu His Asp Glu Ala Tyr Ala Ala 35 40 45 Tyr Leu Arg Ser Gly Lys Asn ProTyr Leu Tyr Phe Ser Pro Ala Asp 50 55 60 Gln Arg Phe Ile Asp Gln Thr LysAsp Ala Thr Asp Trp Gly Gly Lys 65 70 75 80 Ile Gly His Tyr Phe Phe ArgAla Lys Lys Ala Ile Ala Pro Val Leu 85 90 95 Thr Asp Thr Pro Asp His ProSer Thr Ser Arg Pro Thr Lys Pro Thr 100 105 110 Lys Arg Ser Lys Pro ProPro His Ile Phe Ile Asn Leu Ala Lys Lys 115 120 125 Lys Lys Ala Gly AlaGly Gln Val Lys Arg Asp Asn Gln Ala Pro Met 130 135 140 Ser Asp Gly AlaVal Gln Pro Asp Gly Gly Gln Pro Ala Val Arg Asn 145 150 155 160 Glu ArgAla Thr Gly Ser Gly Asn Gly Ser Gly Gly Gly Gly Gly Gly 165 170 175 GlySer Gly Gly Val Gly Ile Ser Thr Gly Thr Phe Asn Asn Gln Thr 180 185 190Glu Phe Lys Phe Leu Glu Asn Gly Trp Val Glu Ile Thr Ala Asn Ser 195 200205 Ser Arg Leu Val His Leu Asn Met Pro Glu Ser Glu Asn Tyr Lys Arg 210215 220 Val Val Val Asn Asn Met Asp Lys Thr Ala Val Lys Gly Asn Met Ala225 230 235 240 Leu Asp Asp Thr His Val Gln Ile Val Thr Pro Trp Ser LeuVal Asp 245 250 255 Ala Asn Ala Trp Gly Val Trp Phe Asn Pro Gly Asp TrpGln Leu Ile 260 265 270 Val Asn Thr Met Ser Glu Leu His Leu Val Ser PheGlu Gln Glu Ile 275 280 285 Phe Asn Val Val Leu Lys Thr Val Ser Glu SerAla Thr Gln Pro Pro 290 295 300 Thr Lys Val Tyr Asn Asn Asp Leu Thr AlaSer Leu Met Val Ala Leu 305 310 315 320 Asp Ser Asn Asn Thr Met Pro PheThr Pro Ala Ala Met Arg Ser Glu 325 330 335 Thr Leu Gly Phe Tyr Pro TrpLys Pro Thr Ile Pro Thr Pro Trp Arg 340 345 350 Tyr Tyr Phe Gln Trp AspArg Thr Leu Ile Pro Ser His Thr Gly Thr 355 360 365 Ser Gly Thr Pro ThrAsn Ile Tyr His Gly Thr Asp Pro Asp Asp Val 370 375 380 Gln Phe Tyr ThrIle Glu Asn Ser Val Pro Val His Leu Leu Arg Thr 385 390 395 400 Gly AspGlu Phe Ala Thr Gly Thr Phe Phe Phe Asp Cys Lys Pro Cys 405 410 415 ArgLeu Thr His Thr Trp Gln Thr Asn Arg Ala Leu Gly Leu Pro Pro 420 425 430Phe Leu Asn Ser Leu Pro Gln Ser Glu Gly Ala Thr Asn Phe Gly Asp 435 440445 Ile Gly Val Gln Gln Asp Lys Arg Arg Gly Val Thr Gln Met Gly Asn 450455 460 Thr Asp Tyr Ile Thr Glu Ala Thr Ile Met Arg Pro Ala Glu Val Gly465 470 475 480 Tyr Ser Ala Pro Tyr Tyr Ser Phe Glu Ala Ser Thr Gln GlyPro Phe 485 490 495 Lys Ile Pro Ile Ala Ala Gly Arg Gly Gly Ala Gln ThrAsp Glu Asn 500 505 510 Gln Ala Ala Asp Gly Asp Pro Arg Tyr Ala Phe GlyArg Gln His Gly 515 520 525 Gln Lys Thr Thr Thr Thr Gly Glu Thr Pro GluArg Phe Thr Tyr Ile 530 535 540 Ala His Gln Asp Thr Gly Arg Tyr Pro AlaGly Asp Trp Ile Gln Asn 545 550 555 560 Ile Asn Phe Asn Leu Pro Val ThrAsn Asp Asn Val Leu Leu Pro Thr 565 570 575 Asp Pro Ile Gly Gly Lys ThrGly Ile Asn Tyr Thr Asn Ile Phe Asn 580 585 590 Thr Tyr Gly Pro Leu ThrAla Leu Asn Asn Val Pro Pro Val Tyr Pro 595 600 605 Asn Gly Gln Ile TrpAsp Lys Glu Phe Asp Thr Asp 610 615 620 11 1431 DNA Feline parvovirusCDS (1)..(1431) 11 atg agt gat gga gca gtt caa cca gac ggt ggt caa cctgct gtc aga 48 Met Ser Asp Gly Ala Val Gln Pro Asp Gly Gly Gln Pro AlaVal Arg 1 5 10 15 aat gaa aga gct aca gga tct ggg aac ggg tct gga ggcggg ggt ggt 96 Asn Glu Arg Ala Thr Gly Ser Gly Asn Gly Ser Gly Gly GlyGly Gly 20 25 30 ggt ggt tct ggg ggt gtg ggg att tct acg ggt act ttc aataat cag 144 Gly Gly Ser Gly Gly Val Gly Ile Ser Thr Gly Thr Phe Asn AsnGln 35 40 45 acg gaa ttt aaa ttt ttg gaa aac gga tgg gtg gaa atc aca gcaaac 192 Thr Glu Phe Lys Phe Leu Glu Asn Gly Trp Val Glu Ile Thr Ala Asn50 55 60 tca agc aga ctt gta cat tta aat atg cca gaa agt gaa aat tat aaa240 Ser Ser Arg Leu Val His Leu Asn Met Pro Glu Ser Glu Asn Tyr Lys 6570 75 80 aga gta gtt gta aat aat atg gat aaa act gca gtt aaa gga aac atg288 Arg Val Val Val Asn Asn Met Asp Lys Thr Ala Val Lys Gly Asn Met 8590 95 gct tta gat gac act cat gta caa att gta aca cct tgg tca ttg gtt336 Ala Leu Asp Asp Thr His Val Gln Ile Val Thr Pro Trp Ser Leu Val 100105 110 gat gca aat gct tgg gga gtt tgg ttt aat cca gga gat tgg caa cta384 Asp Ala Asn Ala Trp Gly Val Trp Phe Asn Pro Gly Asp Trp Gln Leu 115120 125 att gtt aat act atg agt gag ttg cat tta gtt agt ttt gaa caa gaa432 Ile Val Asn Thr Met Ser Glu Leu His Leu Val Ser Phe Glu Gln Glu 130135 140 att ttt aat gtt gtt tta aag act gtt tca gaa tct gct act cag cca480 Ile Phe Asn Val Val Leu Lys Thr Val Ser Glu Ser Ala Thr Gln Pro 145150 155 160 cca act aaa gtt tat aat aat gat tta act gca tca ttg atg gttgca 528 Pro Thr Lys Val Tyr Asn Asn Asp Leu Thr Ala Ser Leu Met Val Ala165 170 175 tta gat agt aat aat act atg cca ttt act cca gca gct atg agatct 576 Leu Asp Ser Asn Asn Thr Met Pro Phe Thr Pro Ala Ala Met Arg Ser180 185 190 gag aca ttg ggt ttt tat cca tgg aaa cca acc ata cca act ccatgg 624 Glu Thr Leu Gly Phe Tyr Pro Trp Lys Pro Thr Ile Pro Thr Pro Trp195 200 205 aga tat tat ttt caa tgg gat aga aca tta ata cca tct cat actgga 672 Arg Tyr Tyr Phe Gln Trp Asp Arg Thr Leu Ile Pro Ser His Thr Gly210 215 220 act agt ggc aca cca aca aat ata tat cat ggt aca gat cca gatgat 720 Thr Ser Gly Thr Pro Thr Asn Ile Tyr His Gly Thr Asp Pro Asp Asp225 230 235 240 gtt caa ttt tat act att gaa aat tct gtg cca gta cac ttacta aga 768 Val Gln Phe Tyr Thr Ile Glu Asn Ser Val Pro Val His Leu LeuArg 245 250 255 aca ggt gat gaa ttt gct aca gga aca ttt ttt ttt gat tgtaaa cca 816 Thr Gly Asp Glu Phe Ala Thr Gly Thr Phe Phe Phe Asp Cys LysPro 260 265 270 tgt aga cta aca cat aca tgg caa aca aac aga gca ttg ggctta cca 864 Cys Arg Leu Thr His Thr Trp Gln Thr Asn Arg Ala Leu Gly LeuPro 275 280 285 cca ttt cta aat tct ttg cct caa tct gaa gga gct act aacttt ggt 912 Pro Phe Leu Asn Ser Leu Pro Gln Ser Glu Gly Ala Thr Asn PheGly 290 295 300 gat ata gga gtt caa caa gat aaa aga cgt ggt gta act caaatg gga 960 Asp Ile Gly Val Gln Gln Asp Lys Arg Arg Gly Val Thr Gln MetGly 305 310 315 320 aat aca gac tat att act gaa gct act att atg aga ccagct gag gtt 1008 Asn Thr Asp Tyr Ile Thr Glu Ala Thr Ile Met Arg Pro AlaGlu Val 325 330 335 ggt tat agt gca cca tat tat tct ttt gaa gcg tct acacaa ggg cca 1056 Gly Tyr Ser Ala Pro Tyr Tyr Ser Phe Glu Ala Ser Thr GlnGly Pro 340 345 350 ttt aaa ata cct att gca gca gga cgg ggg gga gcg caaaca gat gaa 1104 Phe Lys Ile Pro Ile Ala Ala Gly Arg Gly Gly Ala Gln ThrAsp Glu 355 360 365 aat caa gca gca gat ggt gat cca aga tat gca ttt ggtaga caa cat 1152 Asn Gln Ala Ala Asp Gly Asp Pro Arg Tyr Ala Phe Gly ArgGln His 370 375 380 ggt caa aaa act act aca aca gga gaa aca cct gag agattt aca tat 1200 Gly Gln Lys Thr Thr Thr Thr Gly Glu Thr Pro Glu Arg PheThr Tyr 385 390 395 400 ata gca cat caa gat aca gga aga tat cca gca ggagat tgg att caa 1248 Ile Ala His Gln Asp Thr Gly Arg Tyr Pro Ala Gly AspTrp Ile Gln 405 410 415 aat att aac ttt aac ctt cct gta aca aat gat aatgta ttg cta cca 1296 Asn Ile Asn Phe Asn Leu Pro Val Thr Asn Asp Asn ValLeu Leu Pro 420 425 430 aca gat cca att gga ggt aaa aca gga atc aac tatact aat ata ttt 1344 Thr Asp Pro Ile Gly Gly Lys Thr Gly Ile Asn Tyr ThrAsn Ile Phe 435 440 445 aat act tat ggt cct tta act gca tta aat aat gtacca cca gtt tat 1392 Asn Thr Tyr Gly Pro Leu Thr Ala Leu Asn Asn Val ProPro Val Tyr 450 455 460 cca aat ggt caa att tgg gat aaa gaa ttt gat actgac 1431 Pro Asn Gly Gln Ile Trp Asp Lys Glu Phe Asp Thr Asp 465 470 47512 477 PRT Feline parvovirus 12 Met Ser Asp Gly Ala Val Gln Pro Asp GlyGly Gln Pro Ala Val Arg 1 5 10 15 Asn Glu Arg Ala Thr Gly Ser Gly AsnGly Ser Gly Gly Gly Gly Gly 20 25 30 Gly Gly Ser Gly Gly Val Gly Ile SerThr Gly Thr Phe Asn Asn Gln 35 40 45 Thr Glu Phe Lys Phe Leu Glu Asn GlyTrp Val Glu Ile Thr Ala Asn 50 55 60 Ser Ser Arg Leu Val His Leu Asn MetPro Glu Ser Glu Asn Tyr Lys 65 70 75 80 Arg Val Val Val Asn Asn Met AspLys Thr Ala Val Lys Gly Asn Met 85 90 95 Ala Leu Asp Asp Thr His Val GlnIle Val Thr Pro Trp Ser Leu Val 100 105 110 Asp Ala Asn Ala Trp Gly ValTrp Phe Asn Pro Gly Asp Trp Gln Leu 115 120 125 Ile Val Asn Thr Met SerGlu Leu His Leu Val Ser Phe Glu Gln Glu 130 135 140 Ile Phe Asn Val ValLeu Lys Thr Val Ser Glu Ser Ala Thr Gln Pro 145 150 155 160 Pro Thr LysVal Tyr Asn Asn Asp Leu Thr Ala Ser Leu Met Val Ala 165 170 175 Leu AspSer Asn Asn Thr Met Pro Phe Thr Pro Ala Ala Met Arg Ser 180 185 190 GluThr Leu Gly Phe Tyr Pro Trp Lys Pro Thr Ile Pro Thr Pro Trp 195 200 205Arg Tyr Tyr Phe Gln Trp Asp Arg Thr Leu Ile Pro Ser His Thr Gly 210 215220 Thr Ser Gly Thr Pro Thr Asn Ile Tyr His Gly Thr Asp Pro Asp Asp 225230 235 240 Val Gln Phe Tyr Thr Ile Glu Asn Ser Val Pro Val His Leu LeuArg 245 250 255 Thr Gly Asp Glu Phe Ala Thr Gly Thr Phe Phe Phe Asp CysLys Pro 260 265 270 Cys Arg Leu Thr His Thr Trp Gln Thr Asn Arg Ala LeuGly Leu Pro 275 280 285 Pro Phe Leu Asn Ser Leu Pro Gln Ser Glu Gly AlaThr Asn Phe Gly 290 295 300 Asp Ile Gly Val Gln Gln Asp Lys Arg Arg GlyVal Thr Gln Met Gly 305 310 315 320 Asn Thr Asp Tyr Ile Thr Glu Ala ThrIle Met Arg Pro Ala Glu Val 325 330 335 Gly Tyr Ser Ala Pro Tyr Tyr SerPhe Glu Ala Ser Thr Gln Gly Pro 340 345 350 Phe Lys Ile Pro Ile Ala AlaGly Arg Gly Gly Ala Gln Thr Asp Glu 355 360 365 Asn Gln Ala Ala Asp GlyAsp Pro Arg Tyr Ala Phe Gly Arg Gln His 370 375 380 Gly Gln Lys Thr ThrThr Thr Gly Glu Thr Pro Glu Arg Phe Thr Tyr 385 390 395 400 Ile Ala HisGln Asp Thr Gly Arg Tyr Pro Ala Gly Asp Trp Ile Gln 405 410 415 Asn IleAsn Phe Asn Leu Pro Val Thr Asn Asp Asn Val Leu Leu Pro 420 425 430 ThrAsp Pro Ile Gly Gly Lys Thr Gly Ile Asn Tyr Thr Asn Ile Phe 435 440 445Asn Thr Tyr Gly Pro Leu Thr Ala Leu Asn Asn Val Pro Pro Val Tyr 450 455460 Pro Asn Gly Gln Ile Trp Asp Lys Glu Phe Asp Thr Asp 465 470 475 132829 DNA Feline herpesvirus 1 CDS (1)..(2829) 13 atg tcc act cgt ggc gatctt ggg aag cgg cga cga ggg agt cgt tgg 48 Met Ser Thr Arg Gly Asp LeuGly Lys Arg Arg Arg Gly Ser Arg Trp 1 5 10 15 cag gga cac agt ggc tatttt cga cag aga tgt ttt ttc cct tct cta 96 Gln Gly His Ser Gly Tyr PheArg Gln Arg Cys Phe Phe Pro Ser Leu 20 25 30 ctc ggt att gca gcg act ggctcc aga cat ggt aac gga tcg tcg gga 144 Leu Gly Ile Ala Ala Thr Gly SerArg His Gly Asn Gly Ser Ser Gly 35 40 45 tta acc aga cta gct aga tat gtttca ttt atc tgg atc gta cta ttc 192 Leu Thr Arg Leu Ala Arg Tyr Val SerPhe Ile Trp Ile Val Leu Phe 50 55 60 tta gtc ggt ccc cgt cca gta gag ggtcaa tct gga agc aca tcg gaa 240 Leu Val Gly Pro Arg Pro Val Glu Gly GlnSer Gly Ser Thr Ser Glu 65 70 75 80 caa ccc cgg cgg act gta gct acc cctgag gta ggg gta cac cac caa 288 Gln Pro Arg Arg Thr Val Ala Thr Pro GluVal Gly Val His His Gln 85 90 95 aac caa cta cag atc cca ccg ata tgt cgatat gag gaa gct ctc cgt 336 Asn Gln Leu Gln Ile Pro Pro Ile Cys Arg TyrGlu Glu Ala Leu Arg 100 105 110 gcg tcc caa ata gag gct aac gga cca tcgact ttt tat atg tgt cca 384 Ala Ser Gln Ile Glu Ala Asn Gly Pro Ser ThrPhe Tyr Met Cys Pro 115 120 125 cca cct tca gga tct act gtc gtg cgt ttagag cca cca cgg gcc tgt 432 Pro Pro Ser Gly Ser Thr Val Val Arg Leu GluPro Pro Arg Ala Cys 130 135 140 cca gat tat aaa cta ggg aaa aat ttt accgag ggt ata gct gta ata 480 Pro Asp Tyr Lys Leu Gly Lys Asn Phe Thr GluGly Ile Ala Val Ile 145 150 155 160 ttt aaa gaa aat ata gcg cca tat aaattc aag gca aat ata tac tat 528 Phe Lys Glu Asn Ile Ala Pro Tyr Lys PheLys Ala Asn Ile Tyr Tyr 165 170 175 aaa aac att att atg aca acg gta tggtct ggg agt tcc tat gcc gtt 576 Lys Asn Ile Ile Met Thr Thr Val Trp SerGly Ser Ser Tyr Ala Val 180 185 190 aca acc aac cga tat aca gac agg gttccc gtg aaa gtt caa gag att 624 Thr Thr Asn Arg Tyr Thr Asp Arg Val ProVal Lys Val Gln Glu Ile 195 200 205 aca gat ctc ata gat aga cgg ggt atgtgc ctc tcg aaa gct gat tac 672 Thr Asp Leu Ile Asp Arg Arg Gly Met CysLeu Ser Lys Ala Asp Tyr 210 215 220 gtt cgt aac aat tat caa ttt acg gccttt gat cga gac gag gat ccc 720 Val Arg Asn Asn Tyr Gln Phe Thr Ala PheAsp Arg Asp Glu Asp Pro 225 230 235 240 aga gaa ctg cct ctg aaa cct ccaagt tca aca ctc tcc aga gtc cgt 768 Arg Glu Leu Pro Leu Lys Pro Pro SerSer Thr Leu Ser Arg Val Arg 245 250 255 gga tgg cac acc aat gaa aca tacaca aag atc gtg ctg ctg gat ttc 816 Gly Trp His Thr Asn Glu Thr Tyr ThrLys Ile Val Leu Leu Asp Phe 260 265 270 cac cac tct ggg acc tct gta aattgc atc gta gag gaa gtg gat gca 864 His His Ser Gly Thr Ser Val Asn CysIle Val Glu Glu Val Asp Ala 275 280 285 aga tct gta tat cca tat gac tcattt gct atc tcc act ggt gac gtg 912 Arg Ser Val Tyr Pro Tyr Asp Ser PheAla Ile Ser Thr Gly Asp Val 290 295 300 att cac atg tct cca ttc ttt gggctg agg gat gga gcc cat gta gaa 960 Ile His Met Ser Pro Phe Phe Gly LeuArg Asp Gly Ala His Val Glu 305 310 315 320 cat act agt tat tct tca gacaga ttt caa caa atc gag gga tac tat 1008 His Thr Ser Tyr Ser Ser Asp ArgPhe Gln Gln Ile Glu Gly Tyr Tyr 325 330 335 cca ata gac ttg gat acc gattac act ggg gca cca gtt tct cgc aat 1056 Pro Ile Asp Leu Asp Thr Asp TyrThr Gly Ala Pro Val Ser Arg Asn 340 345 350 ttt ttg gaa act ccg cat gtgaca gtg gcc tgg aac tgg acc cca aag 1104 Phe Leu Glu Thr Pro His Val ThrVal Ala Trp Asn Trp Thr Pro Lys 355 360 365 tct ggt cgg gta tgt acc ttagcc aaa tgg agg gaa ata gat gaa atg 1152 Ser Gly Arg Val Cys Thr Leu AlaLys Trp Arg Glu Ile Asp Glu Met 370 375 380 cta ccg atg aat ata ggc tcctat aga ttt aca gcc aag acc ata tcc 1200 Leu Pro Met Asn Ile Gly Ser TyrArg Phe Thr Ala Lys Thr Ile Ser 385 390 395 400 gct act ttc atc tcc aatact tca caa ttt gaa atc aat cgt atc cgt 1248 Ala Thr Phe Ile Ser Asn ThrSer Gln Phe Glu Ile Asn Arg Ile Arg 405 410 415 ttg ggg gac tgt gcc accaag gag gca gcc gaa gcc ata gac cgg att 1296 Leu Gly Asp Cys Ala Thr LysGlu Ala Ala Glu Ala Ile Asp Arg Ile 420 425 430 tat aag agt aaa tat agtaaa act cat att cag act gga acc ctg gag 1344 Tyr Lys Ser Lys Tyr Ser LysThr His Ile Gln Thr Gly Thr Leu Glu 435 440 445 acc tac cta gcc cgt ggggga ttt cta ata gct ttc cgt ccc atg atc 1392 Thr Tyr Leu Ala Arg Gly GlyPhe Leu Ile Ala Phe Arg Pro Met Ile 450 455 460 agc aac gaa cta gca aagtta tat atc aat gaa tta gca cgt tcc aat 1440 Ser Asn Glu Leu Ala Lys LeuTyr Ile Asn Glu Leu Ala Arg Ser Asn 465 470 475 480 cgc acg gta gtg gatctc agt gca ctc ctc aat cca tct ggg gaa aca 1488 Arg Thr Val Val Asp LeuSer Ala Leu Leu Asn Pro Ser Gly Glu Thr 485 490 495 gta caa cga act agaaga tcg gtc cca tct aat caa cat cat agg tcg 1536 Val Gln Arg Thr Arg ArgSer Val Pro Ser Asn Gln His His Arg Ser 500 505 510 cgg cgc agc aca atagag ggg ggt ata gaa acc gtg aac aat gca tca 1584 Arg Arg Ser Thr Ile GluGly Gly Ile Glu Thr Val Asn Asn Ala Ser 515 520 525 ctc ctc aag acc acctca tct gtg gaa ttc gca atg cta caa ttt gcc 1632 Leu Leu Lys Thr Thr SerSer Val Glu Phe Ala Met Leu Gln Phe Ala 530 535 540 tat gac tac ata caagcc cat gta aat gaa atg ttg agt cgg ata gcc 1680 Tyr Asp Tyr Ile Gln AlaHis Val Asn Glu Met Leu Ser Arg Ile Ala 545 550 555 560 act gcc tgg tgtaca ctt cag aac cgc gaa cat gtg ctg tgg aca gag 1728 Thr Ala Trp Cys ThrLeu Gln Asn Arg Glu His Val Leu Trp Thr Glu 565 570 575 acc cta aaa ctcaat ccc ggt ggg gtg gtc tcg atg gcc cta gaa cgt 1776 Thr Leu Lys Leu AsnPro Gly Gly Val Val Ser Met Ala Leu Glu Arg 580 585 590 cgt gta tcc gcgcgc cta ctt gga gat gcc gtc gcc gta aca caa tgt 1824 Arg Val Ser Ala ArgLeu Leu Gly Asp Ala Val Ala Val Thr Gln Cys 595 600 605 gtt aac att tctagc gga cat gtc tat atc caa aat tct atg cgg gtg 1872 Val Asn Ile Ser SerGly His Val Tyr Ile Gln Asn Ser Met Arg Val 610 615 620 acg ggt tca tcaacg aca tgt tac agc cgc cct ctt gtt tcc ttc cgt 1920 Thr Gly Ser Ser ThrThr Cys Tyr Ser Arg Pro Leu Val Ser Phe Arg 625 630 635 640 gcc ctc aatgac tcc gaa tac ata gaa gga caa cta ggg gaa aac aat 1968 Ala Leu Asn AspSer Glu Tyr Ile Glu Gly Gln Leu Gly Glu Asn Asn 645 650 655 gaa ctt ctcgtg gaa cga aaa cta att gag cct tgc act gtc aat aat 2016 Glu Leu Leu ValGlu Arg Lys Leu Ile Glu Pro Cys Thr Val Asn Asn 660 665 670 aag cgg tatttt aag ttt ggg gca gat tat gta tat ttt gag gat tat 2064 Lys Arg Tyr PheLys Phe Gly Ala Asp Tyr Val Tyr Phe Glu Asp Tyr 675 680 685 gcg tat gtccgt aaa gtc ccg cta tcg gag ata gaa ctg ata agt gcg 2112 Ala Tyr Val ArgLys Val Pro Leu Ser Glu Ile Glu Leu Ile Ser Ala 690 695 700 tat gtg attaaa tct act ctc cta gag gat cgt gaa ttt ctc cac tca 2160 Tyr Val Ile LysSer Thr Leu Leu Glu Asp Arg Glu Phe Leu His Ser 705 710 715 720 agt tataca cga gct gag ctg gaa gat acc ggc cct ttt gac tac agc 2208 Ser Tyr ThrArg Ala Glu Leu Glu Asp Thr Gly Pro Phe Asp Tyr Ser 725 730 735 gag attcaa cgc cgc aac caa ctc cac gcc tta aaa ttt tat gat ata 2256 Glu Ile GlnArg Arg Asn Gln Leu His Ala Leu Lys Phe Tyr Asp Ile 740 745 750 gac agcata gtc aga gtg gat aat aat ctt gtc atc atg cgt ggt atg 2304 Asp Ser IleVal Arg Val Asp Asn Asn Leu Val Ile Met Arg Gly Met 755 760 765 gca aatttt ttt cag gga ctc ggg gat gtg ggg gct ggt ttc ggc aag 2352 Ala Asn PhePhe Gln Gly Leu Gly Asp Val Gly Ala Gly Phe Gly Lys 770 775 780 gtg gtctta ggg gct gcg agt gcg gta atc tca aca gta tca ggc gta 2400 Val Val LeuGly Ala Ala Ser Ala Val Ile Ser Thr Val Ser Gly Val 785 790 795 800 tcatca ttt cta aac aac cca ttt gga gca ttg gcc gtg gga ctg tta 2448 Ser SerPhe Leu Asn Asn Pro Phe Gly Ala Leu Ala Val Gly Leu Leu 805 810 815 atatta gct ggc atc gtc gca gca ttc ctg gca tat cgc tat ata tct 2496 Ile LeuAla Gly Ile Val Ala Ala Phe Leu Ala Tyr Arg Tyr Ile Ser 820 825 830 agatta cgt gca aat cca atg aaa gcc tta tat cct gtg acg act agg 2544 Arg LeuArg Ala Asn Pro Met Lys Ala Leu Tyr Pro Val Thr Thr Arg 835 840 845 aatttg aaa cag acg gct aag agc ccc gcc tca acg gct ggt ggg gat 2592 Asn LeuLys Gln Thr Ala Lys Ser Pro Ala Ser Thr Ala Gly Gly Asp 850 855 860 agcgac ccg gga gtc gat gac ttc gat gag gaa aag cta atg cag gca 2640 Ser AspPro Gly Val Asp Asp Phe Asp Glu Glu Lys Leu Met Gln Ala 865 870 875 880agg gag atg ata aaa tat atg tcc ctc gta tcg gct atg gag caa caa 2688 ArgGlu Met Ile Lys Tyr Met Ser Leu Val Ser Ala Met Glu Gln Gln 885 890 895gaa cat aag gcg atg aaa aag aat aag ggc cca gcg atc cta acg agt 2736 GluHis Lys Ala Met Lys Lys Asn Lys Gly Pro Ala Ile Leu Thr Ser 900 905 910cat ctc act aac atg gcc ctc cgt cgc cgt gga cct aaa tac caa cgc 2784 HisLeu Thr Asn Met Ala Leu Arg Arg Arg Gly Pro Lys Tyr Gln Arg 915 920 925ctc aat aat ctt gat agc ggt gat gat act gaa aca aat ctt gtc 2829 Leu AsnAsn Leu Asp Ser Gly Asp Asp Thr Glu Thr Asn Leu Val 930 935 940 14 943PRT Feline herpesvirus 1 14 Met Ser Thr Arg Gly Asp Leu Gly Lys Arg ArgArg Gly Ser Arg Trp 1 5 10 15 Gln Gly His Ser Gly Tyr Phe Arg Gln ArgCys Phe Phe Pro Ser Leu 20 25 30 Leu Gly Ile Ala Ala Thr Gly Ser Arg HisGly Asn Gly Ser Ser Gly 35 40 45 Leu Thr Arg Leu Ala Arg Tyr Val Ser PheIle Trp Ile Val Leu Phe 50 55 60 Leu Val Gly Pro Arg Pro Val Glu Gly GlnSer Gly Ser Thr Ser Glu 65 70 75 80 Gln Pro Arg Arg Thr Val Ala Thr ProGlu Val Gly Val His His Gln 85 90 95 Asn Gln Leu Gln Ile Pro Pro Ile CysArg Tyr Glu Glu Ala Leu Arg 100 105 110 Ala Ser Gln Ile Glu Ala Asn GlyPro Ser Thr Phe Tyr Met Cys Pro 115 120 125 Pro Pro Ser Gly Ser Thr ValVal Arg Leu Glu Pro Pro Arg Ala Cys 130 135 140 Pro Asp Tyr Lys Leu GlyLys Asn Phe Thr Glu Gly Ile Ala Val Ile 145 150 155 160 Phe Lys Glu AsnIle Ala Pro Tyr Lys Phe Lys Ala Asn Ile Tyr Tyr 165 170 175 Lys Asn IleIle Met Thr Thr Val Trp Ser Gly Ser Ser Tyr Ala Val 180 185 190 Thr ThrAsn Arg Tyr Thr Asp Arg Val Pro Val Lys Val Gln Glu Ile 195 200 205 ThrAsp Leu Ile Asp Arg Arg Gly Met Cys Leu Ser Lys Ala Asp Tyr 210 215 220Val Arg Asn Asn Tyr Gln Phe Thr Ala Phe Asp Arg Asp Glu Asp Pro 225 230235 240 Arg Glu Leu Pro Leu Lys Pro Pro Ser Ser Thr Leu Ser Arg Val Arg245 250 255 Gly Trp His Thr Asn Glu Thr Tyr Thr Lys Ile Val Leu Leu AspPhe 260 265 270 His His Ser Gly Thr Ser Val Asn Cys Ile Val Glu Glu ValAsp Ala 275 280 285 Arg Ser Val Tyr Pro Tyr Asp Ser Phe Ala Ile Ser ThrGly Asp Val 290 295 300 Ile His Met Ser Pro Phe Phe Gly Leu Arg Asp GlyAla His Val Glu 305 310 315 320 His Thr Ser Tyr Ser Ser Asp Arg Phe GlnGln Ile Glu Gly Tyr Tyr 325 330 335 Pro Ile Asp Leu Asp Thr Asp Tyr ThrGly Ala Pro Val Ser Arg Asn 340 345 350 Phe Leu Glu Thr Pro His Val ThrVal Ala Trp Asn Trp Thr Pro Lys 355 360 365 Ser Gly Arg Val Cys Thr LeuAla Lys Trp Arg Glu Ile Asp Glu Met 370 375 380 Leu Pro Met Asn Ile GlySer Tyr Arg Phe Thr Ala Lys Thr Ile Ser 385 390 395 400 Ala Thr Phe IleSer Asn Thr Ser Gln Phe Glu Ile Asn Arg Ile Arg 405 410 415 Leu Gly AspCys Ala Thr Lys Glu Ala Ala Glu Ala Ile Asp Arg Ile 420 425 430 Tyr LysSer Lys Tyr Ser Lys Thr His Ile Gln Thr Gly Thr Leu Glu 435 440 445 ThrTyr Leu Ala Arg Gly Gly Phe Leu Ile Ala Phe Arg Pro Met Ile 450 455 460Ser Asn Glu Leu Ala Lys Leu Tyr Ile Asn Glu Leu Ala Arg Ser Asn 465 470475 480 Arg Thr Val Val Asp Leu Ser Ala Leu Leu Asn Pro Ser Gly Glu Thr485 490 495 Val Gln Arg Thr Arg Arg Ser Val Pro Ser Asn Gln His His ArgSer 500 505 510 Arg Arg Ser Thr Ile Glu Gly Gly Ile Glu Thr Val Asn AsnAla Ser 515 520 525 Leu Leu Lys Thr Thr Ser Ser Val Glu Phe Ala Met LeuGln Phe Ala 530 535 540 Tyr Asp Tyr Ile Gln Ala His Val Asn Glu Met LeuSer Arg Ile Ala 545 550 555 560 Thr Ala Trp Cys Thr Leu Gln Asn Arg GluHis Val Leu Trp Thr Glu 565 570 575 Thr Leu Lys Leu Asn Pro Gly Gly ValVal Ser Met Ala Leu Glu Arg 580 585 590 Arg Val Ser Ala Arg Leu Leu GlyAsp Ala Val Ala Val Thr Gln Cys 595 600 605 Val Asn Ile Ser Ser Gly HisVal Tyr Ile Gln Asn Ser Met Arg Val 610 615 620 Thr Gly Ser Ser Thr ThrCys Tyr Ser Arg Pro Leu Val Ser Phe Arg 625 630 635 640 Ala Leu Asn AspSer Glu Tyr Ile Glu Gly Gln Leu Gly Glu Asn Asn 645 650 655 Glu Leu LeuVal Glu Arg Lys Leu Ile Glu Pro Cys Thr Val Asn Asn 660 665 670 Lys ArgTyr Phe Lys Phe Gly Ala Asp Tyr Val Tyr Phe Glu Asp Tyr 675 680 685 AlaTyr Val Arg Lys Val Pro Leu Ser Glu Ile Glu Leu Ile Ser Ala 690 695 700Tyr Val Ile Lys Ser Thr Leu Leu Glu Asp Arg Glu Phe Leu His Ser 705 710715 720 Ser Tyr Thr Arg Ala Glu Leu Glu Asp Thr Gly Pro Phe Asp Tyr Ser725 730 735 Glu Ile Gln Arg Arg Asn Gln Leu His Ala Leu Lys Phe Tyr AspIle 740 745 750 Asp Ser Ile Val Arg Val Asp Asn Asn Leu Val Ile Met ArgGly Met 755 760 765 Ala Asn Phe Phe Gln Gly Leu Gly Asp Val Gly Ala GlyPhe Gly Lys 770 775 780 Val Val Leu Gly Ala Ala Ser Ala Val Ile Ser ThrVal Ser Gly Val 785 790 795 800 Ser Ser Phe Leu Asn Asn Pro Phe Gly AlaLeu Ala Val Gly Leu Leu 805 810 815 Ile Leu Ala Gly Ile Val Ala Ala PheLeu Ala Tyr Arg Tyr Ile Ser 820 825 830 Arg Leu Arg Ala Asn Pro Met LysAla Leu Tyr Pro Val Thr Thr Arg 835 840 845 Asn Leu Lys Gln Thr Ala LysSer Pro Ala Ser Thr Ala Gly Gly Asp 850 855 860 Ser Asp Pro Gly Val AspAsp Phe Asp Glu Glu Lys Leu Met Gln Ala 865 870 875 880 Arg Glu Met IleLys Tyr Met Ser Leu Val Ser Ala Met Glu Gln Gln 885 890 895 Glu His LysAla Met Lys Lys Asn Lys Gly Pro Ala Ile Leu Thr Ser 900 905 910 His LeuThr Asn Met Ala Leu Arg Arg Arg Gly Pro Lys Tyr Gln Arg 915 920 925 LeuAsn Asn Leu Asp Ser Gly Asp Asp Thr Glu Thr Asn Leu Val 930 935 940 15750 DNA Feline herpesvirus 1 CDS (1)..(750) 15 atg tcc act cgt ggc gatctt ggg aag cgg cga cga ggg agt cgt tgg 48 Met Ser Thr Arg Gly Asp LeuGly Lys Arg Arg Arg Gly Ser Arg Trp 1 5 10 15 cag gga cac agt ggc tatttt cga cag aga tgt ttt ttc cct tct cta 96 Gln Gly His Ser Gly Tyr PheArg Gln Arg Cys Phe Phe Pro Ser Leu 20 25 30 ctc ggt att gca gcg act ggctcc aga cat ggt aac gga tcg tcg gga 144 Leu Gly Ile Ala Ala Thr Gly SerArg His Gly Asn Gly Ser Ser Gly 35 40 45 tta acc aga cta gct aga tat gtttca ttt atc tgg atc gta cta ttc 192 Leu Thr Arg Leu Ala Arg Tyr Val SerPhe Ile Trp Ile Val Leu Phe 50 55 60 tta gtc ggt ccc cgt cca gta gag ggtcaa tct gga agc aca tcg gaa 240 Leu Val Gly Pro Arg Pro Val Glu Gly GlnSer Gly Ser Thr Ser Glu 65 70 75 80 caa ccc cgg cgg act gta gct acc cctgag gta ggg gta cac cac caa 288 Gln Pro Arg Arg Thr Val Ala Thr Pro GluVal Gly Val His His Gln 85 90 95 aac caa cta cag atc cca ccg ata tgt cgatat gag gaa gct ctc cgt 336 Asn Gln Leu Gln Ile Pro Pro Ile Cys Arg TyrGlu Glu Ala Leu Arg 100 105 110 gcg tcc caa ata gag gct aac gga cca tcgact ttt tat atg tgt cca 384 Ala Ser Gln Ile Glu Ala Asn Gly Pro Ser ThrPhe Tyr Met Cys Pro 115 120 125 cca cct tca gga tct act gtc gtg cgt ttagag cca cca cgg gcc tgt 432 Pro Pro Ser Gly Ser Thr Val Val Arg Leu GluPro Pro Arg Ala Cys 130 135 140 cca gat tat aaa cta ggg aaa aat ttt accgag ggt ata gct gta ata 480 Pro Asp Tyr Lys Leu Gly Lys Asn Phe Thr GluGly Ile Ala Val Ile 145 150 155 160 ttt aaa gaa aat ata gcg cca tat aaattc aag gca aat ata tac tat 528 Phe Lys Glu Asn Ile Ala Pro Tyr Lys PheLys Ala Asn Ile Tyr Tyr 165 170 175 aaa aac att att atg aca acg gta tggtct ggg agt tcc tat gcc gtt 576 Lys Asn Ile Ile Met Thr Thr Val Trp SerGly Ser Ser Tyr Ala Val 180 185 190 aca acc aac cga tat aca gac agg gttccc gtg aaa gtt caa gag att 624 Thr Thr Asn Arg Tyr Thr Asp Arg Val ProVal Lys Val Gln Glu Ile 195 200 205 aca gat ctc ata gat aga cgg ggt atgtgc ctc tcg aaa gct gat tac 672 Thr Asp Leu Ile Asp Arg Arg Gly Met CysLeu Ser Lys Ala Asp Tyr 210 215 220 gtt cgt aac aat tat caa ttt acg gccttt gat cga gac gag gat ccc 720 Val Arg Asn Asn Tyr Gln Phe Thr Ala PheAsp Arg Asp Glu Asp Pro 225 230 235 240 aga gaa ctg cct ctg aaa cct ccaagt tca 750 Arg Glu Leu Pro Leu Lys Pro Pro Ser Ser 245 250 16 250 PRTFeline herpesvirus 1 16 Met Ser Thr Arg Gly Asp Leu Gly Lys Arg Arg ArgGly Ser Arg Trp 1 5 10 15 Gln Gly His Ser Gly Tyr Phe Arg Gln Arg CysPhe Phe Pro Ser Leu 20 25 30 Leu Gly Ile Ala Ala Thr Gly Ser Arg His GlyAsn Gly Ser Ser Gly 35 40 45 Leu Thr Arg Leu Ala Arg Tyr Val Ser Phe IleTrp Ile Val Leu Phe 50 55 60 Leu Val Gly Pro Arg Pro Val Glu Gly Gln SerGly Ser Thr Ser Glu 65 70 75 80 Gln Pro Arg Arg Thr Val Ala Thr Pro GluVal Gly Val His His Gln 85 90 95 Asn Gln Leu Gln Ile Pro Pro Ile Cys ArgTyr Glu Glu Ala Leu Arg 100 105 110 Ala Ser Gln Ile Glu Ala Asn Gly ProSer Thr Phe Tyr Met Cys Pro 115 120 125 Pro Pro Ser Gly Ser Thr Val ValArg Leu Glu Pro Pro Arg Ala Cys 130 135 140 Pro Asp Tyr Lys Leu Gly LysAsn Phe Thr Glu Gly Ile Ala Val Ile 145 150 155 160 Phe Lys Glu Asn IleAla Pro Tyr Lys Phe Lys Ala Asn Ile Tyr Tyr 165 170 175 Lys Asn Ile IleMet Thr Thr Val Trp Ser Gly Ser Ser Tyr Ala Val 180 185 190 Thr Thr AsnArg Tyr Thr Asp Arg Val Pro Val Lys Val Gln Glu Ile 195 200 205 Thr AspLeu Ile Asp Arg Arg Gly Met Cys Leu Ser Lys Ala Asp Tyr 210 215 220 ValArg Asn Asn Tyr Gln Phe Thr Ala Phe Asp Arg Asp Glu Asp Pro 225 230 235240 Arg Glu Leu Pro Leu Lys Pro Pro Ser Ser 245 250 17 1602 DNA Felineherpesvirus 1 CDS (1)..(1602) 17 atg aga cga tat agg atg gga cgc gga atctac ctt ctc tat atc tgt 48 Met Arg Arg Tyr Arg Met Gly Arg Gly Ile TyrLeu Leu Tyr Ile Cys 1 5 10 15 ctg tta tat aca tat ctc cag ttt ggt acttcg tcg aca acc gcg gtc 96 Leu Leu Tyr Thr Tyr Leu Gln Phe Gly Thr SerSer Thr Thr Ala Val 20 25 30 agt att gaa aat agt gat aat agt act gcg gagatg tta tca tct acc 144 Ser Ile Glu Asn Ser Asp Asn Ser Thr Ala Glu MetLeu Ser Ser Thr 35 40 45 agc atg tcc gct acc acc ccg ata tcc cag cca acatct cca ttc act 192 Ser Met Ser Ala Thr Thr Pro Ile Ser Gln Pro Thr SerPro Phe Thr 50 55 60 act cca act aga aga tct aca aat ata gct aca agt tcgagt acc acc 240 Thr Pro Thr Arg Arg Ser Thr Asn Ile Ala Thr Ser Ser SerThr Thr 65 70 75 80 cag gca tcc cag cca aca tct aca tta act act cta actaga agc tcg 288 Gln Ala Ser Gln Pro Thr Ser Thr Leu Thr Thr Leu Thr ArgSer Ser 85 90 95 aca act ata gct aca agt ccg agt acc acc cag gca gcc acattc ata 336 Thr Thr Ile Ala Thr Ser Pro Ser Thr Thr Gln Ala Ala Thr PheIle 100 105 110 gga tca tct acc gat tcc aat acc act tta ctc aaa aca acaaaa aaa 384 Gly Ser Ser Thr Asp Ser Asn Thr Thr Leu Leu Lys Thr Thr LysLys 115 120 125 cca aag cgt aaa aag aat aag aat aac ggg gcc aga ttt aaatta tat 432 Pro Lys Arg Lys Lys Asn Lys Asn Asn Gly Ala Arg Phe Lys LeuTyr 130 135 140 tgt gga tat aag ggg gtt atc tac aga ccg tat ttt agc cctctt cag 480 Cys Gly Tyr Lys Gly Val Ile Tyr Arg Pro Tyr Phe Ser Pro LeuGln 145 150 155 160 cta aac tgt act cta ccc aca gaa cct cat att acc aaccct att gac 528 Leu Asn Cys Thr Leu Pro Thr Glu Pro His Ile Thr Asn ProIle Asp 165 170 175 ttc gag atc tgg ttt aaa cca cgc acc aga ttt ggg gatttt ctt ggg 576 Phe Glu Ile Trp Phe Lys Pro Arg Thr Arg Phe Gly Asp PheLeu Gly 180 185 190 gat aaa gaa gac ttc gta ggg aat cat acc cgc acc agcata tta cta 624 Asp Lys Glu Asp Phe Val Gly Asn His Thr Arg Thr Ser IleLeu Leu 195 200 205 ttt agc agc cgt aat ggg agt gtt aat tcc atg gat cttggg gac gcg 672 Phe Ser Ser Arg Asn Gly Ser Val Asn Ser Met Asp Leu GlyAsp Ala 210 215 220 aca ctc ggg atc cta caa tct agg ata cca gat tac acatta tat aat 720 Thr Leu Gly Ile Leu Gln Ser Arg Ile Pro Asp Tyr Thr LeuTyr Asn 225 230 235 240 att ccc ata caa cat acc gaa gcg atg tca ttg ggaatc aaa tct gtg 768 Ile Pro Ile Gln His Thr Glu Ala Met Ser Leu Gly IleLys Ser Val 245 250 255 gaa tct gcc acg tcc ggt gtt tat aca tgg cgg gtctat ggt gga gat 816 Glu Ser Ala Thr Ser Gly Val Tyr Thr Trp Arg Val TyrGly Gly Asp 260 265 270 gta cta aat aaa aca gtg cta gga cag gta aat gtatct gta gtg gca 864 Val Leu Asn Lys Thr Val Leu Gly Gln Val Asn Val SerVal Val Ala 275 280 285 tat cac ccc ccg agc gta aat ctt aca cca cgc gccagt cta ttt aat 912 Tyr His Pro Pro Ser Val Asn Leu Thr Pro Arg Ala SerLeu Phe Asn 290 295 300 aag acc ttt gag gcg gta tgt gca gtg gcg aat tacttc ccc ccg cga 960 Lys Thr Phe Glu Ala Val Cys Ala Val Ala Asn Tyr PhePro Pro Arg 305 310 315 320 tcc acg aaa cta aca tgg tat ctt gac ggg aagcca ata gaa agg caa 1008 Ser Thr Lys Leu Thr Trp Tyr Leu Asp Gly Lys ProIle Glu Arg Gln 325 330 335 tac att tca gat acg gca agt gta tgg ata gatgga ctc atc acc aga 1056 Tyr Ile Ser Asp Thr Ala Ser Val Trp Ile Asp GlyLeu Ile Thr Arg 340 345 350 agt tct gtg ttg gct att ccg aca act gaa acagat tcc gag aaa cca 1104 Ser Ser Val Leu Ala Ile Pro Thr Thr Glu Thr AspSer Glu Lys Pro 355 360 365 gat ata cga tgt gat ttg gaa tgg cat gaa agtcct gtg tcc tat aag 1152 Asp Ile Arg Cys Asp Leu Glu Trp His Glu Ser ProVal Ser Tyr Lys 370 375 380 aga ttc acg aaa agt gta gcc ccg gac gtc tattac cca cct act gtg 1200 Arg Phe Thr Lys Ser Val Ala Pro Asp Val Tyr TyrPro Pro Thr Val 385 390 395 400 tct gtt acc ttc gct gat aca cgg gct atatgt gat gtt aaa tgt gta 1248 Ser Val Thr Phe Ala Asp Thr Arg Ala Ile CysAsp Val Lys Cys Val 405 410 415 cca cgg gac ggg ata tcc ttg atg tgg aaaatt ggt aac tac cat cta 1296 Pro Arg Asp Gly Ile Ser Leu Met Trp Lys IleGly Asn Tyr His Leu 420 425 430 cca aaa gca atg agt gct gat ata ctg atcaca ggt ccg tgt ata gaa 1344 Pro Lys Ala Met Ser Ala Asp Ile Leu Ile ThrGly Pro Cys Ile Glu 435 440 445 cgt cca ggt ttg gtc aac att cag agt atgtgt gat ata tca gaa acg 1392 Arg Pro Gly Leu Val Asn Ile Gln Ser Met CysAsp Ile Ser Glu Thr 450 455 460 gat gga ccc gtg agt tat acc tgt cag accatc gga tac cca cca att 1440 Asp Gly Pro Val Ser Tyr Thr Cys Gln Thr IleGly Tyr Pro Pro Ile 465 470 475 480 cta ccg gga ttt tac gac aca caa gtctac gac gcg tcc cct gaa atc 1488 Leu Pro Gly Phe Tyr Asp Thr Gln Val TyrAsp Ala Ser Pro Glu Ile 485 490 495 gtc agt gaa tca atg ttg gtt agt gtcgtt gct gta ata cta gga gct 1536 Val Ser Glu Ser Met Leu Val Ser Val ValAla Val Ile Leu Gly Ala 500 505 510 gtt ctc atc aca gtc ttt atc ttt attacg gca tta tgt tta tat tat 1584 Val Leu Ile Thr Val Phe Ile Phe Ile ThrAla Leu Cys Leu Tyr Tyr 515 520 525 tct cat ccc cgg cga tta 1602 Ser HisPro Arg Arg Leu 530 18 534 PRT Feline herpesvirus 1 18 Met Arg Arg TyrArg Met Gly Arg Gly Ile Tyr Leu Leu Tyr Ile Cys 1 5 10 15 Leu Leu TyrThr Tyr Leu Gln Phe Gly Thr Ser Ser Thr Thr Ala Val 20 25 30 Ser Ile GluAsn Ser Asp Asn Ser Thr Ala Glu Met Leu Ser Ser Thr 35 40 45 Ser Met SerAla Thr Thr Pro Ile Ser Gln Pro Thr Ser Pro Phe Thr 50 55 60 Thr Pro ThrArg Arg Ser Thr Asn Ile Ala Thr Ser Ser Ser Thr Thr 65 70 75 80 Gln AlaSer Gln Pro Thr Ser Thr Leu Thr Thr Leu Thr Arg Ser Ser 85 90 95 Thr ThrIle Ala Thr Ser Pro Ser Thr Thr Gln Ala Ala Thr Phe Ile 100 105 110 GlySer Ser Thr Asp Ser Asn Thr Thr Leu Leu Lys Thr Thr Lys Lys 115 120 125Pro Lys Arg Lys Lys Asn Lys Asn Asn Gly Ala Arg Phe Lys Leu Tyr 130 135140 Cys Gly Tyr Lys Gly Val Ile Tyr Arg Pro Tyr Phe Ser Pro Leu Gln 145150 155 160 Leu Asn Cys Thr Leu Pro Thr Glu Pro His Ile Thr Asn Pro IleAsp 165 170 175 Phe Glu Ile Trp Phe Lys Pro Arg Thr Arg Phe Gly Asp PheLeu Gly 180 185 190 Asp Lys Glu Asp Phe Val Gly Asn His Thr Arg Thr SerIle Leu Leu 195 200 205 Phe Ser Ser Arg Asn Gly Ser Val Asn Ser Met AspLeu Gly Asp Ala 210 215 220 Thr Leu Gly Ile Leu Gln Ser Arg Ile Pro AspTyr Thr Leu Tyr Asn 225 230 235 240 Ile Pro Ile Gln His Thr Glu Ala MetSer Leu Gly Ile Lys Ser Val 245 250 255 Glu Ser Ala Thr Ser Gly Val TyrThr Trp Arg Val Tyr Gly Gly Asp 260 265 270 Val Leu Asn Lys Thr Val LeuGly Gln Val Asn Val Ser Val Val Ala 275 280 285 Tyr His Pro Pro Ser ValAsn Leu Thr Pro Arg Ala Ser Leu Phe Asn 290 295 300 Lys Thr Phe Glu AlaVal Cys Ala Val Ala Asn Tyr Phe Pro Pro Arg 305 310 315 320 Ser Thr LysLeu Thr Trp Tyr Leu Asp Gly Lys Pro Ile Glu Arg Gln 325 330 335 Tyr IleSer Asp Thr Ala Ser Val Trp Ile Asp Gly Leu Ile Thr Arg 340 345 350 SerSer Val Leu Ala Ile Pro Thr Thr Glu Thr Asp Ser Glu Lys Pro 355 360 365Asp Ile Arg Cys Asp Leu Glu Trp His Glu Ser Pro Val Ser Tyr Lys 370 375380 Arg Phe Thr Lys Ser Val Ala Pro Asp Val Tyr Tyr Pro Pro Thr Val 385390 395 400 Ser Val Thr Phe Ala Asp Thr Arg Ala Ile Cys Asp Val Lys CysVal 405 410 415 Pro Arg Asp Gly Ile Ser Leu Met Trp Lys Ile Gly Asn TyrHis Leu 420 425 430 Pro Lys Ala Met Ser Ala Asp Ile Leu Ile Thr Gly ProCys Ile Glu 435 440 445 Arg Pro Gly Leu Val Asn Ile Gln Ser Met Cys AspIle Ser Glu Thr 450 455 460 Asp Gly Pro Val Ser Tyr Thr Cys Gln Thr IleGly Tyr Pro Pro Ile 465 470 475 480 Leu Pro Gly Phe Tyr Asp Thr Gln ValTyr Asp Ala Ser Pro Glu Ile 485 490 495 Val Ser Glu Ser Met Leu Val SerVal Val Ala Val Ile Leu Gly Ala 500 505 510 Val Leu Ile Thr Val Phe IlePhe Ile Thr Ala Leu Cys Leu Tyr Tyr 515 520 525 Ser His Pro Arg Arg Leu530 19 1401 DNA Feline herpesvirus 1 CDS (1)..(1401) 19 agt att gaa aatagt gat aat agt act gcg gag atg tta tca tct acc 48 Ser Ile Glu Asn SerAsp Asn Ser Thr Ala Glu Met Leu Ser Ser Thr 1 5 10 15 agc atg tcc gctacc acc ccg ata tcc cag cca aca tct cca ttc act 96 Ser Met Ser Ala ThrThr Pro Ile Ser Gln Pro Thr Ser Pro Phe Thr 20 25 30 act cca act aga agatct aca aat ata gct aca agt tcg agt acc acc 144 Thr Pro Thr Arg Arg SerThr Asn Ile Ala Thr Ser Ser Ser Thr Thr 35 40 45 cag gca tcc cag cca acatct aca tta act act cta act aga agc tcg 192 Gln Ala Ser Gln Pro Thr SerThr Leu Thr Thr Leu Thr Arg Ser Ser 50 55 60 aca act ata gct aca agt ccgagt acc acc cag gca gcc aca ttc ata 240 Thr Thr Ile Ala Thr Ser Pro SerThr Thr Gln Ala Ala Thr Phe Ile 65 70 75 80 gga tca tct acc gat tcc aatacc act tta ctc aaa aca aca aaa aaa 288 Gly Ser Ser Thr Asp Ser Asn ThrThr Leu Leu Lys Thr Thr Lys Lys 85 90 95 cca aag cgt aaa aag aat aag aataac ggg gcc aga ttt aaa tta tat 336 Pro Lys Arg Lys Lys Asn Lys Asn AsnGly Ala Arg Phe Lys Leu Tyr 100 105 110 tgt gga tat aag ggg gtt atc tacaga ccg tat ttt agc cct ctt cag 384 Cys Gly Tyr Lys Gly Val Ile Tyr ArgPro Tyr Phe Ser Pro Leu Gln 115 120 125 cta aac tgt act cta ccc aca gaacct cat att acc aac cct att gac 432 Leu Asn Cys Thr Leu Pro Thr Glu ProHis Ile Thr Asn Pro Ile Asp 130 135 140 ttc gag atc tgg ttt aaa cca cgcacc aga ttt ggg gat ttt ctt ggg 480 Phe Glu Ile Trp Phe Lys Pro Arg ThrArg Phe Gly Asp Phe Leu Gly 145 150 155 160 gat aaa gaa gac ttc gta gggaat cat acc cgc acc agc ata tta cta 528 Asp Lys Glu Asp Phe Val Gly AsnHis Thr Arg Thr Ser Ile Leu Leu 165 170 175 ttt agc agc cgt aat ggg agtgtt aat tcc atg gat ctt ggg gac gcg 576 Phe Ser Ser Arg Asn Gly Ser ValAsn Ser Met Asp Leu Gly Asp Ala 180 185 190 aca ctc ggg atc cta caa tctagg ata cca gat tac aca tta tat aat 624 Thr Leu Gly Ile Leu Gln Ser ArgIle Pro Asp Tyr Thr Leu Tyr Asn 195 200 205 att ccc ata caa cat acc gaagcg atg tca ttg gga atc aaa tct gtg 672 Ile Pro Ile Gln His Thr Glu AlaMet Ser Leu Gly Ile Lys Ser Val 210 215 220 gaa tct gcc acg tcc ggt gtttat aca tgg cgg gtc tat ggt gga gat 720 Glu Ser Ala Thr Ser Gly Val TyrThr Trp Arg Val Tyr Gly Gly Asp 225 230 235 240 gta cta aat aaa aca gtgcta gga cag gta aat gta tct gta gtg gca 768 Val Leu Asn Lys Thr Val LeuGly Gln Val Asn Val Ser Val Val Ala 245 250 255 tat cac ccc ccg agc gtaaat ctt aca cca cgc gcc agt cta ttt aat 816 Tyr His Pro Pro Ser Val AsnLeu Thr Pro Arg Ala Ser Leu Phe Asn 260 265 270 aag acc ttt gag gcg gtatgt gca gtg gcg aat tac ttc ccc ccg cga 864 Lys Thr Phe Glu Ala Val CysAla Val Ala Asn Tyr Phe Pro Pro Arg 275 280 285 tcc acg aaa cta aca tggtat ctt gac ggg aag cca ata gaa agg caa 912 Ser Thr Lys Leu Thr Trp TyrLeu Asp Gly Lys Pro Ile Glu Arg Gln 290 295 300 tac att tca gat acg gcaagt gta tgg ata gat gga ctc atc acc aga 960 Tyr Ile Ser Asp Thr Ala SerVal Trp Ile Asp Gly Leu Ile Thr Arg 305 310 315 320 agt tct gtg ttg gctatt ccg aca act gaa aca gat tcc gag aaa cca 1008 Ser Ser Val Leu Ala IlePro Thr Thr Glu Thr Asp Ser Glu Lys Pro 325 330 335 gat ata cga tgt gatttg gaa tgg cat gaa agt cct gtg tcc tat aag 1056 Asp Ile Arg Cys Asp LeuGlu Trp His Glu Ser Pro Val Ser Tyr Lys 340 345 350 aga ttc acg aaa agtgta gcc ccg gac gtc tat tac cca cct act gtg 1104 Arg Phe Thr Lys Ser ValAla Pro Asp Val Tyr Tyr Pro Pro Thr Val 355 360 365 tct gtt acc ttc gctgat aca cgg gct ata tgt gat gtt aaa tgt gta 1152 Ser Val Thr Phe Ala AspThr Arg Ala Ile Cys Asp Val Lys Cys Val 370 375 380 cca cgg gac ggg atatcc ttg atg tgg aaa att ggt aac tac cat cta 1200 Pro Arg Asp Gly Ile SerLeu Met Trp Lys Ile Gly Asn Tyr His Leu 385 390 395 400 cca aaa gca atgagt gct gat ata ctg atc aca ggt ccg tgt ata gaa 1248 Pro Lys Ala Met SerAla Asp Ile Leu Ile Thr Gly Pro Cys Ile Glu 405 410 415 cgt cca ggt ttggtc aac att cag agt atg tgt gat ata tca gaa acg 1296 Arg Pro Gly Leu ValAsn Ile Gln Ser Met Cys Asp Ile Ser Glu Thr 420 425 430 gat gga ccc gtgagt tat acc tgt cag acc atc gga tac cca cca att 1344 Asp Gly Pro Val SerTyr Thr Cys Gln Thr Ile Gly Tyr Pro Pro Ile 435 440 445 cta ccg gga ttttac gac aca caa gtc tac gac gcg tcc cct gaa atc 1392 Leu Pro Gly Phe TyrAsp Thr Gln Val Tyr Asp Ala Ser Pro Glu Ile 450 455 460 gtc agt gaa 1401Val Ser Glu 465 20 467 PRT Feline herpesvirus 1 20 Ser Ile Glu Asn SerAsp Asn Ser Thr Ala Glu Met Leu Ser Ser Thr 1 5 10 15 Ser Met Ser AlaThr Thr Pro Ile Ser Gln Pro Thr Ser Pro Phe Thr 20 25 30 Thr Pro Thr ArgArg Ser Thr Asn Ile Ala Thr Ser Ser Ser Thr Thr 35 40 45 Gln Ala Ser GlnPro Thr Ser Thr Leu Thr Thr Leu Thr Arg Ser Ser 50 55 60 Thr Thr Ile AlaThr Ser Pro Ser Thr Thr Gln Ala Ala Thr Phe Ile 65 70 75 80 Gly Ser SerThr Asp Ser Asn Thr Thr Leu Leu Lys Thr Thr Lys Lys 85 90 95 Pro Lys ArgLys Lys Asn Lys Asn Asn Gly Ala Arg Phe Lys Leu Tyr 100 105 110 Cys GlyTyr Lys Gly Val Ile Tyr Arg Pro Tyr Phe Ser Pro Leu Gln 115 120 125 LeuAsn Cys Thr Leu Pro Thr Glu Pro His Ile Thr Asn Pro Ile Asp 130 135 140Phe Glu Ile Trp Phe Lys Pro Arg Thr Arg Phe Gly Asp Phe Leu Gly 145 150155 160 Asp Lys Glu Asp Phe Val Gly Asn His Thr Arg Thr Ser Ile Leu Leu165 170 175 Phe Ser Ser Arg Asn Gly Ser Val Asn Ser Met Asp Leu Gly AspAla 180 185 190 Thr Leu Gly Ile Leu Gln Ser Arg Ile Pro Asp Tyr Thr LeuTyr Asn 195 200 205 Ile Pro Ile Gln His Thr Glu Ala Met Ser Leu Gly IleLys Ser Val 210 215 220 Glu Ser Ala Thr Ser Gly Val Tyr Thr Trp Arg ValTyr Gly Gly Asp 225 230 235 240 Val Leu Asn Lys Thr Val Leu Gly Gln ValAsn Val Ser Val Val Ala 245 250 255 Tyr His Pro Pro Ser Val Asn Leu ThrPro Arg Ala Ser Leu Phe Asn 260 265 270 Lys Thr Phe Glu Ala Val Cys AlaVal Ala Asn Tyr Phe Pro Pro Arg 275 280 285 Ser Thr Lys Leu Thr Trp TyrLeu Asp Gly Lys Pro Ile Glu Arg Gln 290 295 300 Tyr Ile Ser Asp Thr AlaSer Val Trp Ile Asp Gly Leu Ile Thr Arg 305 310 315 320 Ser Ser Val LeuAla Ile Pro Thr Thr Glu Thr Asp Ser Glu Lys Pro 325 330 335 Asp Ile ArgCys Asp Leu Glu Trp His Glu Ser Pro Val Ser Tyr Lys 340 345 350 Arg PheThr Lys Ser Val Ala Pro Asp Val Tyr Tyr Pro Pro Thr Val 355 360 365 SerVal Thr Phe Ala Asp Thr Arg Ala Ile Cys Asp Val Lys Cys Val 370 375 380Pro Arg Asp Gly Ile Ser Leu Met Trp Lys Ile Gly Asn Tyr His Leu 385 390395 400 Pro Lys Ala Met Ser Ala Asp Ile Leu Ile Thr Gly Pro Cys Ile Glu405 410 415 Arg Pro Gly Leu Val Asn Ile Gln Ser Met Cys Asp Ile Ser GluThr 420 425 430 Asp Gly Pro Val Ser Tyr Thr Cys Gln Thr Ile Gly Tyr ProPro Ile 435 440 445 Leu Pro Gly Phe Tyr Asp Thr Gln Val Tyr Asp Ala SerPro Glu Ile 450 455 460 Val Ser Glu 465 21 1401 DNA Feline herpesvirus 1CDS (1)..(1401) 21 atg tcc atc gaa aac agc gat aat agt act gcg gag atgtta tca tct 48 Met Ser Ile Glu Asn Ser Asp Asn Ser Thr Ala Glu Met LeuSer Ser 1 5 10 15 acc agc atg tcc gct acc acc ccg ata tcc cag cca acatct cca ttc 96 Thr Ser Met Ser Ala Thr Thr Pro Ile Ser Gln Pro Thr SerPro Phe 20 25 30 act act cca act cgt cgc tct aca aat ata gct aca tcc tcttcc acc 144 Thr Thr Pro Thr Arg Arg Ser Thr Asn Ile Ala Thr Ser Ser SerThr 35 40 45 acc cag gca tcc cag cca aca tct aca tta act act cta act agaagc 192 Thr Gln Ala Ser Gln Pro Thr Ser Thr Leu Thr Thr Leu Thr Arg Ser50 55 60 tcg aca act ata gct aca agt ccg agt acc acc cag gca gcc aca ttc240 Ser Thr Thr Ile Ala Thr Ser Pro Ser Thr Thr Gln Ala Ala Thr Phe 6570 75 80 ata gga tca tct acc gat tcc aat acc act tta ctc aaa aca aca aaa288 Ile Gly Ser Ser Thr Asp Ser Asn Thr Thr Leu Leu Lys Thr Thr Lys 8590 95 aaa cca aag cgt aaa aag aat aag aat aac ggg gcc aga ttt aaa tta336 Lys Pro Lys Arg Lys Lys Asn Lys Asn Asn Gly Ala Arg Phe Lys Leu 100105 110 gat tgt gga tat aag ggg gtt atc tac aga ccg tat ttt agc cct ctt384 Asp Cys Gly Tyr Lys Gly Val Ile Tyr Arg Pro Tyr Phe Ser Pro Leu 115120 125 cag cta aac tgt act cta ccc aca gaa cct cat att acc aac cct att432 Gln Leu Asn Cys Thr Leu Pro Thr Glu Pro His Ile Thr Asn Pro Ile 130135 140 gac ttc gag atc tgg ttt aaa cca cgc acc aga ttt ggg gat ttt ctt480 Asp Phe Glu Ile Trp Phe Lys Pro Arg Thr Arg Phe Gly Asp Phe Leu 145150 155 160 ggg gat aaa gaa gac ttc gta ggg aat cat acc cgc acc agc atatta 528 Gly Asp Lys Glu Asp Phe Val Gly Asn His Thr Arg Thr Ser Ile Leu165 170 175 cta ttt agc agc cgt aat ggg agt gtt aat tcc atg gat ctt ggggac 576 Leu Phe Ser Ser Arg Asn Gly Ser Val Asn Ser Met Asp Leu Gly Asp180 185 190 gcg aca ctc ggg atc cta caa tct agg ata cca gat tac aca ttatat 624 Ala Thr Leu Gly Ile Leu Gln Ser Arg Ile Pro Asp Tyr Thr Leu Tyr195 200 205 aat att ccc ata caa cat acc gaa gcg atg tca ttg gga atc aaatct 672 Asn Ile Pro Ile Gln His Thr Glu Ala Met Ser Leu Gly Ile Lys Ser210 215 220 gtg gaa tct gcc act tct ggt gtt tat aca tgg cgt gtc tat ggtgga 720 Val Glu Ser Ala Thr Ser Gly Val Tyr Thr Trp Arg Val Tyr Gly Gly225 230 235 240 gat ggt ctg aac aaa aca gtg ctg ggt cag gta aat gta tctgta gtg 768 Asp Gly Leu Asn Lys Thr Val Leu Gly Gln Val Asn Val Ser ValVal 245 250 255 gca tat cac ccc ccg agc gta aat ctt aca cca cgc gcc agtcta ttt 816 Ala Tyr His Pro Pro Ser Val Asn Leu Thr Pro Arg Ala Ser LeuPhe 260 265 270 aat aag acc ttt gag gcg gta tgt gca gtg gcg aat tac ttcccc ccg 864 Asn Lys Thr Phe Glu Ala Val Cys Ala Val Ala Asn Tyr Phe ProPro 275 280 285 cga tcc acg aaa cta aca tgg tat ctt gac ggg aag cca atagaa agg 912 Arg Ser Thr Lys Leu Thr Trp Tyr Leu Asp Gly Lys Pro Ile GluArg 290 295 300 caa tac att tca gat acg gca agt gta tgg ata gat gga ctcatc acc 960 Gln Tyr Ile Ser Asp Thr Ala Ser Val Trp Ile Asp Gly Leu IleThr 305 310 315 320 aga agt tct gtg ttg gct att ccg aca act gaa aca gattcc gag aaa 1008 Arg Ser Ser Val Leu Ala Ile Pro Thr Thr Glu Thr Asp SerGlu Lys 325 330 335 cca gat ata cga tgt gat ttg gaa tgg cat gaa agt cctgtg tcc tat 1056 Pro Asp Ile Arg Cys Asp Leu Glu Trp His Glu Ser Pro ValSer Tyr 340 345 350 aag aga ttc acg aaa agt gta gcc ccg gac gtc tat taccca cct act 1104 Lys Arg Phe Thr Lys Ser Val Ala Pro Asp Val Tyr Tyr ProPro Thr 355 360 365 gtg tct gtt acc ttc gct gat aca cgg gct ata tgt gatgtt aaa tgt 1152 Val Ser Val Thr Phe Ala Asp Thr Arg Ala Ile Cys Asp ValLys Cys 370 375 380 gta cca cgg gac ggg ata tcc ttg atg tgg aaa att ggtaac tac cat 1200 Val Pro Arg Asp Gly Ile Ser Leu Met Trp Lys Ile Gly AsnTyr His 385 390 395 400 cta cca aaa gca atg agt gct gat ata ctg atc acaggt ccg tgt ata 1248 Leu Pro Lys Ala Met Ser Ala Asp Ile Leu Ile Thr GlyPro Cys Ile 405 410 415 gaa cgt cca ggt ttg gtc aac att cag agt atg tgtgat ata tca gaa 1296 Glu Arg Pro Gly Leu Val Asn Ile Gln Ser Met Cys AspIle Ser Glu 420 425 430 acg gat gga ccc gtg agt tat acc tgt cag acc atcgga tac cca cca 1344 Thr Asp Gly Pro Val Ser Tyr Thr Cys Gln Thr Ile GlyTyr Pro Pro 435 440 445 att cta ccg gga ttt tac gac aca caa gtc tac gacgcg tcc cct gaa 1392 Ile Leu Pro Gly Phe Tyr Asp Thr Gln Val Tyr Asp AlaSer Pro Glu 450 455 460 atc gtc tcc 1401 Ile Val Ser 465 22 467 PRTFeline herpesvirus 1 22 Met Ser Ile Glu Asn Ser Asp Asn Ser Thr Ala GluMet Leu Ser Ser 1 5 10 15 Thr Ser Met Ser Ala Thr Thr Pro Ile Ser GlnPro Thr Ser Pro Phe 20 25 30 Thr Thr Pro Thr Arg Arg Ser Thr Asn Ile AlaThr Ser Ser Ser Thr 35 40 45 Thr Gln Ala Ser Gln Pro Thr Ser Thr Leu ThrThr Leu Thr Arg Ser 50 55 60 Ser Thr Thr Ile Ala Thr Ser Pro Ser Thr ThrGln Ala Ala Thr Phe 65 70 75 80 Ile Gly Ser Ser Thr Asp Ser Asn Thr ThrLeu Leu Lys Thr Thr Lys 85 90 95 Lys Pro Lys Arg Lys Lys Asn Lys Asn AsnGly Ala Arg Phe Lys Leu 100 105 110 Asp Cys Gly Tyr Lys Gly Val Ile TyrArg Pro Tyr Phe Ser Pro Leu 115 120 125 Gln Leu Asn Cys Thr Leu Pro ThrGlu Pro His Ile Thr Asn Pro Ile 130 135 140 Asp Phe Glu Ile Trp Phe LysPro Arg Thr Arg Phe Gly Asp Phe Leu 145 150 155 160 Gly Asp Lys Glu AspPhe Val Gly Asn His Thr Arg Thr Ser Ile Leu 165 170 175 Leu Phe Ser SerArg Asn Gly Ser Val Asn Ser Met Asp Leu Gly Asp 180 185 190 Ala Thr LeuGly Ile Leu Gln Ser Arg Ile Pro Asp Tyr Thr Leu Tyr 195 200 205 Asn IlePro Ile Gln His Thr Glu Ala Met Ser Leu Gly Ile Lys Ser 210 215 220 ValGlu Ser Ala Thr Ser Gly Val Tyr Thr Trp Arg Val Tyr Gly Gly 225 230 235240 Asp Gly Leu Asn Lys Thr Val Leu Gly Gln Val Asn Val Ser Val Val 245250 255 Ala Tyr His Pro Pro Ser Val Asn Leu Thr Pro Arg Ala Ser Leu Phe260 265 270 Asn Lys Thr Phe Glu Ala Val Cys Ala Val Ala Asn Tyr Phe ProPro 275 280 285 Arg Ser Thr Lys Leu Thr Trp Tyr Leu Asp Gly Lys Pro IleGlu Arg 290 295 300 Gln Tyr Ile Ser Asp Thr Ala Ser Val Trp Ile Asp GlyLeu Ile Thr 305 310 315 320 Arg Ser Ser Val Leu Ala Ile Pro Thr Thr GluThr Asp Ser Glu Lys 325 330 335 Pro Asp Ile Arg Cys Asp Leu Glu Trp HisGlu Ser Pro Val Ser Tyr 340 345 350 Lys Arg Phe Thr Lys Ser Val Ala ProAsp Val Tyr Tyr Pro Pro Thr 355 360 365 Val Ser Val Thr Phe Ala Asp ThrArg Ala Ile Cys Asp Val Lys Cys 370 375 380 Val Pro Arg Asp Gly Ile SerLeu Met Trp Lys Ile Gly Asn Tyr His 385 390 395 400 Leu Pro Lys Ala MetSer Ala Asp Ile Leu Ile Thr Gly Pro Cys Ile 405 410 415 Glu Arg Pro GlyLeu Val Asn Ile Gln Ser Met Cys Asp Ile Ser Glu 420 425 430 Thr Asp GlyPro Val Ser Tyr Thr Cys Gln Thr Ile Gly Tyr Pro Pro 435 440 445 Ile LeuPro Gly Phe Tyr Asp Thr Gln Val Tyr Asp Ala Ser Pro Glu 450 455 460 IleVal Ser 465 23 1122 DNA Feline herpesvirus 1 CDS (1)..(1122) 23 atg atgaca cgt cta cat ttt tgg tgg tgt gga atc ttt gcg gtc ctg 48 Met Met ThrArg Leu His Phe Trp Trp Cys Gly Ile Phe Ala Val Leu 1 5 10 15 aaa tatctg gta tgt act tca agc ctt acg acc acg cca aaa aca act 96 Lys Tyr LeuVal Cys Thr Ser Ser Leu Thr Thr Thr Pro Lys Thr Thr 20 25 30 acg gtt tatgtg aag gga ttt aat ata cct cca cta cgc tac aat tat 144 Thr Val Tyr ValLys Gly Phe Asn Ile Pro Pro Leu Arg Tyr Asn Tyr 35 40 45 act caa gcc agaatc gtg cca aaa att ccc cag gcg atg gat ccg aag 192 Thr Gln Ala Arg IleVal Pro Lys Ile Pro Gln Ala Met Asp Pro Lys 50 55 60 ata aca gct gaa gtacgt tat gta aca tca atg gat tca tgt ggg atg 240 Ile Thr Ala Glu Val ArgTyr Val Thr Ser Met Asp Ser Cys Gly Met 65 70 75 80 gtg gca ttg ata tcagag ccg gat ata gac gct act att cga acc ata 288 Val Ala Leu Ile Ser GluPro Asp Ile Asp Ala Thr Ile Arg Thr Ile 85 90 95 caa cta tct caa aaa aaaaca tat aac gcg act ata agt tgg ttt aag 336 Gln Leu Ser Gln Lys Lys ThrTyr Asn Ala Thr Ile Ser Trp Phe Lys 100 105 110 gta acc cag ggt tgt gaatac cct atg ttt ctt atg gat atg aga ctt 384 Val Thr Gln Gly Cys Glu TyrPro Met Phe Leu Met Asp Met Arg Leu 115 120 125 tgt gat cct aaa cgg gaattt gga ata tgt gct tta cgg tcg cct tca 432 Cys Asp Pro Lys Arg Glu PheGly Ile Cys Ala Leu Arg Ser Pro Ser 130 135 140 tat tgg ttg gaa cct ttaaca aag tat atg ttc cta aca gac gat gaa 480 Tyr Trp Leu Glu Pro Leu ThrLys Tyr Met Phe Leu Thr Asp Asp Glu 145 150 155 160 ctg ggt ttg att atgatg gcc ccg gcc caa ttt aat caa gga caa tat 528 Leu Gly Leu Ile Met MetAla Pro Ala Gln Phe Asn Gln Gly Gln Tyr 165 170 175 cga aga gtt ata accatc gat ggt tcc atg ttt tat aca gat ttt atg 576 Arg Arg Val Ile Thr IleAsp Gly Ser Met Phe Tyr Thr Asp Phe Met 180 185 190 gta caa cta tct ccaacg cca tgt tgg ttc gca aaa ccc gat aga tac 624 Val Gln Leu Ser Pro ThrPro Cys Trp Phe Ala Lys Pro Asp Arg Tyr 195 200 205 gaa gag att cta catgaa tgg tgt cga aat gtt aaa act att ggc ctt 672 Glu Glu Ile Leu His GluTrp Cys Arg Asn Val Lys Thr Ile Gly Leu 210 215 220 gat gga gct cgt gattac cac tat tat tgg gta ccc tat aac cca caa 720 Asp Gly Ala Arg Asp TyrHis Tyr Tyr Trp Val Pro Tyr Asn Pro Gln 225 230 235 240 cct cac cat aaagcc gta ctc tta tat tgg tat cgg act cat ggc cga 768 Pro His His Lys AlaVal Leu Leu Tyr Trp Tyr Arg Thr His Gly Arg 245 250 255 gaa ccc cca gtaaga ttc caa gag gcc att cga tat gat cgt ccc gcc 816 Glu Pro Pro Val ArgPhe Gln Glu Ala Ile Arg Tyr Asp Arg Pro Ala 260 265 270 ata ccg tct gggagt gag gat tcg aaa cgg tcc aac gac tct aga gga 864 Ile Pro Ser Gly SerGlu Asp Ser Lys Arg Ser Asn Asp Ser Arg Gly 275 280 285 gaa tcg agt ggaccc aat tgg ata gac att gaa aat tac act cct aaa 912 Glu Ser Ser Gly ProAsn Trp Ile Asp Ile Glu Asn Tyr Thr Pro Lys 290 295 300 aat aat gtg cctatt ata ata tct gac gat gac gtt cct aca gcc cct 960 Asn Asn Val Pro IleIle Ile Ser Asp Asp Asp Val Pro Thr Ala Pro 305 310 315 320 ccc aag ggcatg aat aat cag tca gta gtg ata ccc gca atc gta cta 1008 Pro Lys Gly MetAsn Asn Gln Ser Val Val Ile Pro Ala Ile Val Leu 325 330 335 agt tgt cttata ata gca ctg att cta gga gtg ata tat tat att ttg 1056 Ser Cys Leu IleIle Ala Leu Ile Leu Gly Val Ile Tyr Tyr Ile Leu 340 345 350 agg gta aagagg tct cga tca act gca tat caa caa ctt cct ata ata 1104 Arg Val Lys ArgSer Arg Ser Thr Ala Tyr Gln Gln Leu Pro Ile Ile 355 360 365 cat aca actcac cat cct 1122 His Thr Thr His His Pro 370 24 374 PRT Felineherpesvirus 1 24 Met Met Thr Arg Leu His Phe Trp Trp Cys Gly Ile Phe AlaVal Leu 1 5 10 15 Lys Tyr Leu Val Cys Thr Ser Ser Leu Thr Thr Thr ProLys Thr Thr 20 25 30 Thr Val Tyr Val Lys Gly Phe Asn Ile Pro Pro Leu ArgTyr Asn Tyr 35 40 45 Thr Gln Ala Arg Ile Val Pro Lys Ile Pro Gln Ala MetAsp Pro Lys 50 55 60 Ile Thr Ala Glu Val Arg Tyr Val Thr Ser Met Asp SerCys Gly Met 65 70 75 80 Val Ala Leu Ile Ser Glu Pro Asp Ile Asp Ala ThrIle Arg Thr Ile 85 90 95 Gln Leu Ser Gln Lys Lys Thr Tyr Asn Ala Thr IleSer Trp Phe Lys 100 105 110 Val Thr Gln Gly Cys Glu Tyr Pro Met Phe LeuMet Asp Met Arg Leu 115 120 125 Cys Asp Pro Lys Arg Glu Phe Gly Ile CysAla Leu Arg Ser Pro Ser 130 135 140 Tyr Trp Leu Glu Pro Leu Thr Lys TyrMet Phe Leu Thr Asp Asp Glu 145 150 155 160 Leu Gly Leu Ile Met Met AlaPro Ala Gln Phe Asn Gln Gly Gln Tyr 165 170 175 Arg Arg Val Ile Thr IleAsp Gly Ser Met Phe Tyr Thr Asp Phe Met 180 185 190 Val Gln Leu Ser ProThr Pro Cys Trp Phe Ala Lys Pro Asp Arg Tyr 195 200 205 Glu Glu Ile LeuHis Glu Trp Cys Arg Asn Val Lys Thr Ile Gly Leu 210 215 220 Asp Gly AlaArg Asp Tyr His Tyr Tyr Trp Val Pro Tyr Asn Pro Gln 225 230 235 240 ProHis His Lys Ala Val Leu Leu Tyr Trp Tyr Arg Thr His Gly Arg 245 250 255Glu Pro Pro Val Arg Phe Gln Glu Ala Ile Arg Tyr Asp Arg Pro Ala 260 265270 Ile Pro Ser Gly Ser Glu Asp Ser Lys Arg Ser Asn Asp Ser Arg Gly 275280 285 Glu Ser Ser Gly Pro Asn Trp Ile Asp Ile Glu Asn Tyr Thr Pro Lys290 295 300 Asn Asn Val Pro Ile Ile Ile Ser Asp Asp Asp Val Pro Thr AlaPro 305 310 315 320 Pro Lys Gly Met Asn Asn Gln Ser Val Val Ile Pro AlaIle Val Leu 325 330 335 Ser Cys Leu Ile Ile Ala Leu Ile Leu Gly Val IleTyr Tyr Ile Leu 340 345 350 Arg Val Lys Arg Ser Arg Ser Thr Ala Tyr GlnGln Leu Pro Ile Ile 355 360 365 His Thr Thr His His Pro 370 25 900 DNAFeline herpesvirus 1 CDS (1)..(900) 25 cca aaa aca act acg gtt tat gtgaag gga ttt aat ata cct cca cta 48 Pro Lys Thr Thr Thr Val Tyr Val LysGly Phe Asn Ile Pro Pro Leu 1 5 10 15 cgc tac aat tat act caa gcc agaatc gtg cca aaa att ccc cag gcg 96 Arg Tyr Asn Tyr Thr Gln Ala Arg IleVal Pro Lys Ile Pro Gln Ala 20 25 30 atg gat ccg aag ata aca gct gaa gtacgt tat gta aca tca atg gat 144 Met Asp Pro Lys Ile Thr Ala Glu Val ArgTyr Val Thr Ser Met Asp 35 40 45 tca tgt ggg atg gtg gca ttg ata tca gagccg gat ata gac gct act 192 Ser Cys Gly Met Val Ala Leu Ile Ser Glu ProAsp Ile Asp Ala Thr 50 55 60 att cga acc ata caa cta tct caa aaa aaa acatat aac gcg act ata 240 Ile Arg Thr Ile Gln Leu Ser Gln Lys Lys Thr TyrAsn Ala Thr Ile 65 70 75 80 agt tgg ttt aag gta acc cag ggt tgt gaa taccct atg ttt ctt atg 288 Ser Trp Phe Lys Val Thr Gln Gly Cys Glu Tyr ProMet Phe Leu Met 85 90 95 gat atg aga ctt tgt gat cct aaa cgg gaa ttt ggaata tgt gct tta 336 Asp Met Arg Leu Cys Asp Pro Lys Arg Glu Phe Gly IleCys Ala Leu 100 105 110 cgg tcg cct tca tat tgg ttg gaa cct tta aca aagtat atg ttc cta 384 Arg Ser Pro Ser Tyr Trp Leu Glu Pro Leu Thr Lys TyrMet Phe Leu 115 120 125 aca gac gat gaa ctg ggt ttg att atg atg gcc ccggcc caa ttt aat 432 Thr Asp Asp Glu Leu Gly Leu Ile Met Met Ala Pro AlaGln Phe Asn 130 135 140 caa gga caa tat cga aga gtt ata acc atc gat ggttcc atg ttt tat 480 Gln Gly Gln Tyr Arg Arg Val Ile Thr Ile Asp Gly SerMet Phe Tyr 145 150 155 160 aca gat ttt atg gta caa cta tct cca acg ccatgt tgg ttc gca aaa 528 Thr Asp Phe Met Val Gln Leu Ser Pro Thr Pro CysTrp Phe Ala Lys 165 170 175 ccc gat aga tac gaa gag att cta cat gaa tggtgt cga aat gtt aaa 576 Pro Asp Arg Tyr Glu Glu Ile Leu His Glu Trp CysArg Asn Val Lys 180 185 190 act att ggc ctt gat gga gct cgt gat tac cactat tat tgg gta ccc 624 Thr Ile Gly Leu Asp Gly Ala Arg Asp Tyr His TyrTyr Trp Val Pro 195 200 205 tat aac cca caa cct cac cat aaa gcc gta ctctta tat tgg tat cgg 672 Tyr Asn Pro Gln Pro His His Lys Ala Val Leu LeuTyr Trp Tyr Arg 210 215 220 act cat ggc cga gaa ccc cca gta aga ttc caagag gcc att cga tat 720 Thr His Gly Arg Glu Pro Pro Val Arg Phe Gln GluAla Ile Arg Tyr 225 230 235 240 gat cgt ccc gcc ata ccg tct ggg agt gaggat tcg aaa cgg tcc aac 768 Asp Arg Pro Ala Ile Pro Ser Gly Ser Glu AspSer Lys Arg Ser Asn 245 250 255 gac tct aga gga gaa tcg agt gga ccc aattgg ata gac att gaa aat 816 Asp Ser Arg Gly Glu Ser Ser Gly Pro Asn TrpIle Asp Ile Glu Asn 260 265 270 tac act cct aaa aat aat gtg cct att ataata tct gac gat gac gtt 864 Tyr Thr Pro Lys Asn Asn Val Pro Ile Ile IleSer Asp Asp Asp Val 275 280 285 cct aca gcc cct ccc aag ggc atg aat aatcag tca 900 Pro Thr Ala Pro Pro Lys Gly Met Asn Asn Gln Ser 290 295 30026 300 PRT Feline herpesvirus 1 26 Pro Lys Thr Thr Thr Val Tyr Val LysGly Phe Asn Ile Pro Pro Leu 1 5 10 15 Arg Tyr Asn Tyr Thr Gln Ala ArgIle Val Pro Lys Ile Pro Gln Ala 20 25 30 Met Asp Pro Lys Ile Thr Ala GluVal Arg Tyr Val Thr Ser Met Asp 35 40 45 Ser Cys Gly Met Val Ala Leu IleSer Glu Pro Asp Ile Asp Ala Thr 50 55 60 Ile Arg Thr Ile Gln Leu Ser GlnLys Lys Thr Tyr Asn Ala Thr Ile 65 70 75 80 Ser Trp Phe Lys Val Thr GlnGly Cys Glu Tyr Pro Met Phe Leu Met 85 90 95 Asp Met Arg Leu Cys Asp ProLys Arg Glu Phe Gly Ile Cys Ala Leu 100 105 110 Arg Ser Pro Ser Tyr TrpLeu Glu Pro Leu Thr Lys Tyr Met Phe Leu 115 120 125 Thr Asp Asp Glu LeuGly Leu Ile Met Met Ala Pro Ala Gln Phe Asn 130 135 140 Gln Gly Gln TyrArg Arg Val Ile Thr Ile Asp Gly Ser Met Phe Tyr 145 150 155 160 Thr AspPhe Met Val Gln Leu Ser Pro Thr Pro Cys Trp Phe Ala Lys 165 170 175 ProAsp Arg Tyr Glu Glu Ile Leu His Glu Trp Cys Arg Asn Val Lys 180 185 190Thr Ile Gly Leu Asp Gly Ala Arg Asp Tyr His Tyr Tyr Trp Val Pro 195 200205 Tyr Asn Pro Gln Pro His His Lys Ala Val Leu Leu Tyr Trp Tyr Arg 210215 220 Thr His Gly Arg Glu Pro Pro Val Arg Phe Gln Glu Ala Ile Arg Tyr225 230 235 240 Asp Arg Pro Ala Ile Pro Ser Gly Ser Glu Asp Ser Lys ArgSer Asn 245 250 255 Asp Ser Arg Gly Glu Ser Ser Gly Pro Asn Trp Ile AspIle Glu Asn 260 265 270 Tyr Thr Pro Lys Asn Asn Val Pro Ile Ile Ile SerAsp Asp Asp Val 275 280 285 Pro Thr Ala Pro Pro Lys Gly Met Asn Asn GlnSer 290 295 300 27 759 DNA Feline leukemia virus CDS (1)..(759) 27 atgccg ctg cgt gaa ggt ccg aac aac cgt ccc cag tat tgg cca ttc 48 Met ProLeu Arg Glu Gly Pro Asn Asn Arg Pro Gln Tyr Trp Pro Phe 1 5 10 15 tcagct tca gac ctg tat aac tgg aag tcg cat aac ccc cct ttc tcc 96 Ser AlaSer Asp Leu Tyr Asn Trp Lys Ser His Asn Pro Pro Phe Ser 20 25 30 caa gacccc gtg gcc cta act aac cta att gag tcc att tta gtg acg 144 Gln Asp ProVal Ala Leu Thr Asn Leu Ile Glu Ser Ile Leu Val Thr 35 40 45 cat caa ccaacc tgg gac gac tgc cag caa ctc ttg cag gca ctc ctg 192 His Gln Pro ThrTrp Asp Asp Cys Gln Gln Leu Leu Gln Ala Leu Leu 50 55 60 aca ggc gaa gaaagg caa agg gtc ctt ctt gag gcc cga aag cag gtt 240 Thr Gly Glu Glu ArgGln Arg Val Leu Leu Glu Ala Arg Lys Gln Val 65 70 75 80 cca ggc gag gacgga cgg cca acc cag ctg ccc aat gtc att gac gaa 288 Pro Gly Glu Asp GlyArg Pro Thr Gln Leu Pro Asn Val Ile Asp Glu 85 90 95 gct ttc ccc ttg acccgt ccc aac tgg gat ttt gct acg ccg gca ggt 336 Ala Phe Pro Leu Thr ArgPro Asn Trp Asp Phe Ala Thr Pro Ala Gly 100 105 110 agg gag cac cta cgcctt tat cgc cag ttg ctg tta gcg ggt ctc cgc 384 Arg Glu His Leu Arg LeuTyr Arg Gln Leu Leu Leu Ala Gly Leu Arg 115 120 125 ggg gct gca aga cgcccc act aat ttg gca cag gta aag caa gtt gta 432 Gly Ala Ala Arg Arg ProThr Asn Leu Ala Gln Val Lys Gln Val Val 130 135 140 caa ggg aaa gag gaaacg cca gcc tca ttc tta gaa aga tta aaa gag 480 Gln Gly Lys Glu Glu ThrPro Ala Ser Phe Leu Glu Arg Leu Lys Glu 145 150 155 160 gct tac aga atgtat act ccc tat gac cct gag gac cca ggg cag gct 528 Ala Tyr Arg Met TyrThr Pro Tyr Asp Pro Glu Asp Pro Gly Gln Ala 165 170 175 gct agt gtt atcctg tcc ttt atc tac cag tct agc ccg gac ata aga 576 Ala Ser Val Ile LeuSer Phe Ile Tyr Gln Ser Ser Pro Asp Ile Arg 180 185 190 aat aag tta caaagg cta gaa ggc cta cag ggg ttc aca ctg tct gat 624 Asn Lys Leu Gln ArgLeu Glu Gly Leu Gln Gly Phe Thr Leu Ser Asp 195 200 205 ttg cta aaa gaggca gaa aag ata tac aac aaa agg gag acc cca gag 672 Leu Leu Lys Glu AlaGlu Lys Ile Tyr Asn Lys Arg Glu Thr Pro Glu 210 215 220 gaa agg gaa gaaaga tta tgg cag cgg cag gaa gaa aga gat aaa aag 720 Glu Arg Glu Glu ArgLeu Trp Gln Arg Gln Glu Glu Arg Asp Lys Lys 225 230 235 240 cgc cat aaggag atg act aag gtc tgt gag aat tct agc 759 Arg His Lys Glu Met Thr LysVal Cys Glu Asn Ser Ser 245 250 28 253 PRT Feline leukemia virus 28 MetPro Leu Arg Glu Gly Pro Asn Asn Arg Pro Gln Tyr Trp Pro Phe 1 5 10 15Ser Ala Ser Asp Leu Tyr Asn Trp Lys Ser His Asn Pro Pro Phe Ser 20 25 30Gln Asp Pro Val Ala Leu Thr Asn Leu Ile Glu Ser Ile Leu Val Thr 35 40 45His Gln Pro Thr Trp Asp Asp Cys Gln Gln Leu Leu Gln Ala Leu Leu 50 55 60Thr Gly Glu Glu Arg Gln Arg Val Leu Leu Glu Ala Arg Lys Gln Val 65 70 7580 Pro Gly Glu Asp Gly Arg Pro Thr Gln Leu Pro Asn Val Ile Asp Glu 85 9095 Ala Phe Pro Leu Thr Arg Pro Asn Trp Asp Phe Ala Thr Pro Ala Gly 100105 110 Arg Glu His Leu Arg Leu Tyr Arg Gln Leu Leu Leu Ala Gly Leu Arg115 120 125 Gly Ala Ala Arg Arg Pro Thr Asn Leu Ala Gln Val Lys Gln ValVal 130 135 140 Gln Gly Lys Glu Glu Thr Pro Ala Ser Phe Leu Glu Arg LeuLys Glu 145 150 155 160 Ala Tyr Arg Met Tyr Thr Pro Tyr Asp Pro Glu AspPro Gly Gln Ala 165 170 175 Ala Ser Val Ile Leu Ser Phe Ile Tyr Gln SerSer Pro Asp Ile Arg 180 185 190 Asn Lys Leu Gln Arg Leu Glu Gly Leu GlnGly Phe Thr Leu Ser Asp 195 200 205 Leu Leu Lys Glu Ala Glu Lys Ile TyrAsn Lys Arg Glu Thr Pro Glu 210 215 220 Glu Arg Glu Glu Arg Leu Trp GlnArg Gln Glu Glu Arg Asp Lys Lys 225 230 235 240 Arg His Lys Glu Met ThrLys Val Cys Glu Asn Ser Ser 245 250 29 1830 DNA Feline leukemia virusCDS (1)..(1830) 29 atg gcc aat cct agt cca ccc caa atg tat aat gta acttgg gta ata 48 Met Ala Asn Pro Ser Pro Pro Gln Met Tyr Asn Val Thr TrpVal Ile 1 5 10 15 acc aat gta caa acc aac acc caa gct aat gcc acc tctatg tta gga 96 Thr Asn Val Gln Thr Asn Thr Gln Ala Asn Ala Thr Ser MetLeu Gly 20 25 30 acc tta acc gat gtc tac cct acc cta cat gtt gac tta tgtgac cta 144 Thr Leu Thr Asp Val Tyr Pro Thr Leu His Val Asp Leu Cys AspLeu 35 40 45 gtg gga gac acc tgg gaa cct atg gtc cta agc cca acc ggg taccct 192 Val Gly Asp Thr Trp Glu Pro Met Val Leu Ser Pro Thr Gly Tyr Pro50 55 60 ccc tca aaa tat gga tgt aaa act aca gat aga aaa aaa cag caa cag240 Pro Ser Lys Tyr Gly Cys Lys Thr Thr Asp Arg Lys Lys Gln Gln Gln 6570 75 80 aca tac ccc ttt tac gtc tgc ccc ggg cat cgc ccc tcg ctg ggg cca288 Thr Tyr Pro Phe Tyr Val Cys Pro Gly His Arg Pro Ser Leu Gly Pro 8590 95 aag gga aca cat tgt gga ggg gca caa gat ggg ttt tgt gcc gca tgg336 Lys Gly Thr His Cys Gly Gly Ala Gln Asp Gly Phe Cys Ala Ala Trp 100105 110 gga tgt gaa acc acc gga gaa gct tgg tgg aag ccc tcc tcc tca tgg384 Gly Cys Glu Thr Thr Gly Glu Ala Trp Trp Lys Pro Ser Ser Ser Trp 115120 125 gac tat atc aca gta aaa aga ggg agt agt cag aac aat aac tgt gag432 Asp Tyr Ile Thr Val Lys Arg Gly Ser Ser Gln Asn Asn Asn Cys Glu 130135 140 gga aaa tgc aac ccc ctg att ttg cag ttc acc cag aag ggg aaa caa480 Gly Lys Cys Asn Pro Leu Ile Leu Gln Phe Thr Gln Lys Gly Lys Gln 145150 155 160 gcc tct tgg gac gga cct aag atg tgg gga ttg cgg cta tac cgtaca 528 Ala Ser Trp Asp Gly Pro Lys Met Trp Gly Leu Arg Leu Tyr Arg Thr165 170 175 gga tat gac cct atc gcc tta ttc acg gta tcc cgg cgg gtg tcaacc 576 Gly Tyr Asp Pro Ile Ala Leu Phe Thr Val Ser Arg Arg Val Ser Thr180 185 190 att acg ccg cct cag gca atg gga cca gac cta gtc tta cct gatcaa 624 Ile Thr Pro Pro Gln Ala Met Gly Pro Asp Leu Val Leu Pro Asp Gln195 200 205 aaa ccc cca tcc cga caa tct caa aca ggg tcc aaa gtg gcg acccag 672 Lys Pro Pro Ser Arg Gln Ser Gln Thr Gly Ser Lys Val Ala Thr Gln210 215 220 agg ccc caa acg aat gaa agc gcc cca agg tct gtt gcc ccc accacc 720 Arg Pro Gln Thr Asn Glu Ser Ala Pro Arg Ser Val Ala Pro Thr Thr225 230 235 240 gtg ggt ccc aaa cgg att ggg acc gga gat agg tta ata aattta gta 768 Val Gly Pro Lys Arg Ile Gly Thr Gly Asp Arg Leu Ile Asn LeuVal 245 250 255 caa ggg gca tac cta gcc tta aat gcc acc gac ccc aac aaaact aaa 816 Gln Gly Ala Tyr Leu Ala Leu Asn Ala Thr Asp Pro Asn Lys ThrLys 260 265 270 gac tgt tgg ctc tgc ctg gtt tct cga cca ccc tat tac gaaggg att 864 Asp Cys Trp Leu Cys Leu Val Ser Arg Pro Pro Tyr Tyr Glu GlyIle 275 280 285 gca atc tta ggt aac tac agc aac caa aca aac cct ccc ccatcc tgc 912 Ala Ile Leu Gly Asn Tyr Ser Asn Gln Thr Asn Pro Pro Pro SerCys 290 295 300 cta tct att ccg cca cac aag ctg acc ata tct aaa gta tcaggg caa 960 Leu Ser Ile Pro Pro His Lys Leu Thr Ile Ser Lys Val Ser GlyGln 305 310 315 320 gga ctg tgc ata ggg act gtt cct aag acc cac cag gctttg tgc aat 1008 Gly Leu Cys Ile Gly Thr Val Pro Lys Thr His Gln Ala LeuCys Asn 325 330 335 aag acg cac cag gga cat aca ggg gcg gac tat cga gccgcc ccg cgg 1056 Lys Thr His Gln Gly His Thr Gly Ala Asp Tyr Arg Ala AlaPro Arg 340 345 350 tat cta gcc gcc ccc aat ggc acc tat tgg gcc tgt aacact gga ctc 1104 Tyr Leu Ala Ala Pro Asn Gly Thr Tyr Trp Ala Cys Asn ThrGly Leu 355 360 365 acc cca tgc att tcc atg gcg gtg ctc aat ttg acc tctgat ttt tgt 1152 Thr Pro Cys Ile Ser Met Ala Val Leu Asn Leu Thr Ser AspPhe Cys 370 375 380 gtc tta atc gaa tta tgg ccc aga gtg act tac cat caaccc gaa tat 1200 Val Leu Ile Glu Leu Trp Pro Arg Val Thr Tyr His Gln ProGlu Tyr 385 390 395 400 gtg tac aca cat ttt gcc aaa gct ggc agg ttc cgaaga gaa cca ata 1248 Val Tyr Thr His Phe Ala Lys Ala Gly Arg Phe Arg ArgGlu Pro Ile 405 410 415 tca cta act gtt gcc ctc atg ttg gga gga ctc actgta ggg ggc ata 1296 Ser Leu Thr Val Ala Leu Met Leu Gly Gly Leu Thr ValGly Gly Ile 420 425 430 gcc gcg ggg gtc gga aca ggg act aaa gcc ctc cttgaa aca gcc cag 1344 Ala Ala Gly Val Gly Thr Gly Thr Lys Ala Leu Leu GluThr Ala Gln 435 440 445 ttc aga caa cta caa atg gcc atg cac aca gac atccag gcc cta gaa 1392 Phe Arg Gln Leu Gln Met Ala Met His Thr Asp Ile GlnAla Leu Glu 450 455 460 gag tca att agt gcc tta gaa aag tcc ctg acc tccctt tct gaa gta 1440 Glu Ser Ile Ser Ala Leu Glu Lys Ser Leu Thr Ser LeuSer Glu Val 465 470 475 480 gtc tta caa aac aga cgg ggc cta gat att ctattc cta caa gag gga 1488 Val Leu Gln Asn Arg Arg Gly Leu Asp Ile Leu PheLeu Gln Glu Gly 485 490 495 ggg ctc tgt gcc gca tta aaa gaa gaa tgt tgcttc tat gcg gat cac 1536 Gly Leu Cys Ala Ala Leu Lys Glu Glu Cys Cys PheTyr Ala Asp His 500 505 510 acc gga ctc gtc cga gac aat atg gct aaa ttaaga gaa aga cta aaa 1584 Thr Gly Leu Val Arg Asp Asn Met Ala Lys Leu ArgGlu Arg Leu Lys 515 520 525 cag cgg caa caa ctg ttt gac tcc caa cag ggatgg ttt gaa gga tgg 1632 Gln Arg Gln Gln Leu Phe Asp Ser Gln Gln Gly TrpPhe Glu Gly Trp 530 535 540 ttc aac agg tcc ccc tgg ttt aca acc cta atttcc tcc att atg ggc 1680 Phe Asn Arg Ser Pro Trp Phe Thr Thr Leu Ile SerSer Ile Met Gly 545 550 555 560 ccc tta cta atc cta ctc cta att ctc ctcttc ggc cca tac atc ctt 1728 Pro Leu Leu Ile Leu Leu Leu Ile Leu Leu PheGly Pro Tyr Ile Leu 565 570 575 aac aga tta gta caa ttc gta aaa gac agaata tct gtg gta caa gcc 1776 Asn Arg Leu Val Gln Phe Val Lys Asp Arg IleSer Val Val Gln Ala 580 585 590 tta att tta acc caa cag tac caa cag ataaag caa tac gat ccg gac 1824 Leu Ile Leu Thr Gln Gln Tyr Gln Gln Ile LysGln Tyr Asp Pro Asp 595 600 605 cga cca 1830 Arg Pro 610 30 610 PRTFeline leukemia virus 30 Met Ala Asn Pro Ser Pro Pro Gln Met Tyr Asn ValThr Trp Val Ile 1 5 10 15 Thr Asn Val Gln Thr Asn Thr Gln Ala Asn AlaThr Ser Met Leu Gly 20 25 30 Thr Leu Thr Asp Val Tyr Pro Thr Leu His ValAsp Leu Cys Asp Leu 35 40 45 Val Gly Asp Thr Trp Glu Pro Met Val Leu SerPro Thr Gly Tyr Pro 50 55 60 Pro Ser Lys Tyr Gly Cys Lys Thr Thr Asp ArgLys Lys Gln Gln Gln 65 70 75 80 Thr Tyr Pro Phe Tyr Val Cys Pro Gly HisArg Pro Ser Leu Gly Pro 85 90 95 Lys Gly Thr His Cys Gly Gly Ala Gln AspGly Phe Cys Ala Ala Trp 100 105 110 Gly Cys Glu Thr Thr Gly Glu Ala TrpTrp Lys Pro Ser Ser Ser Trp 115 120 125 Asp Tyr Ile Thr Val Lys Arg GlySer Ser Gln Asn Asn Asn Cys Glu 130 135 140 Gly Lys Cys Asn Pro Leu IleLeu Gln Phe Thr Gln Lys Gly Lys Gln 145 150 155 160 Ala Ser Trp Asp GlyPro Lys Met Trp Gly Leu Arg Leu Tyr Arg Thr 165 170 175 Gly Tyr Asp ProIle Ala Leu Phe Thr Val Ser Arg Arg Val Ser Thr 180 185 190 Ile Thr ProPro Gln Ala Met Gly Pro Asp Leu Val Leu Pro Asp Gln 195 200 205 Lys ProPro Ser Arg Gln Ser Gln Thr Gly Ser Lys Val Ala Thr Gln 210 215 220 ArgPro Gln Thr Asn Glu Ser Ala Pro Arg Ser Val Ala Pro Thr Thr 225 230 235240 Val Gly Pro Lys Arg Ile Gly Thr Gly Asp Arg Leu Ile Asn Leu Val 245250 255 Gln Gly Ala Tyr Leu Ala Leu Asn Ala Thr Asp Pro Asn Lys Thr Lys260 265 270 Asp Cys Trp Leu Cys Leu Val Ser Arg Pro Pro Tyr Tyr Glu GlyIle 275 280 285 Ala Ile Leu Gly Asn Tyr Ser Asn Gln Thr Asn Pro Pro ProSer Cys 290 295 300 Leu Ser Ile Pro Pro His Lys Leu Thr Ile Ser Lys ValSer Gly Gln 305 310 315 320 Gly Leu Cys Ile Gly Thr Val Pro Lys Thr HisGln Ala Leu Cys Asn 325 330 335 Lys Thr His Gln Gly His Thr Gly Ala AspTyr Arg Ala Ala Pro Arg 340 345 350 Tyr Leu Ala Ala Pro Asn Gly Thr TyrTrp Ala Cys Asn Thr Gly Leu 355 360 365 Thr Pro Cys Ile Ser Met Ala ValLeu Asn Leu Thr Ser Asp Phe Cys 370 375 380 Val Leu Ile Glu Leu Trp ProArg Val Thr Tyr His Gln Pro Glu Tyr 385 390 395 400 Val Tyr Thr His PheAla Lys Ala Gly Arg Phe Arg Arg Glu Pro Ile 405 410 415 Ser Leu Thr ValAla Leu Met Leu Gly Gly Leu Thr Val Gly Gly Ile 420 425 430 Ala Ala GlyVal Gly Thr Gly Thr Lys Ala Leu Leu Glu Thr Ala Gln 435 440 445 Phe ArgGln Leu Gln Met Ala Met His Thr Asp Ile Gln Ala Leu Glu 450 455 460 GluSer Ile Ser Ala Leu Glu Lys Ser Leu Thr Ser Leu Ser Glu Val 465 470 475480 Val Leu Gln Asn Arg Arg Gly Leu Asp Ile Leu Phe Leu Gln Glu Gly 485490 495 Gly Leu Cys Ala Ala Leu Lys Glu Glu Cys Cys Phe Tyr Ala Asp His500 505 510 Thr Gly Leu Val Arg Asp Asn Met Ala Lys Leu Arg Glu Arg LeuLys 515 520 525 Gln Arg Gln Gln Leu Phe Asp Ser Gln Gln Gly Trp Phe GluGly Trp 530 535 540 Phe Asn Arg Ser Pro Trp Phe Thr Thr Leu Ile Ser SerIle Met Gly 545 550 555 560 Pro Leu Leu Ile Leu Leu Leu Ile Leu Leu PheGly Pro Tyr Ile Leu 565 570 575 Asn Arg Leu Val Gln Phe Val Lys Asp ArgIle Ser Val Val Gln Ala 580 585 590 Leu Ile Leu Thr Gln Gln Tyr Gln GlnIle Lys Gln Tyr Asp Pro Asp 595 600 605 Arg Pro 610 31 1833 DNA Felineleukemia virus CDS (1)..(1833) 31 atg gag cac cta cgc ctt tat cgc cagttg ctg tta gcg ggt ctc cgc 48 Met Glu His Leu Arg Leu Tyr Arg Gln LeuLeu Leu Ala Gly Leu Arg 1 5 10 15 ggg gct gca aga cac ccc act aat ttggca cag gtt aag caa ttt tta 96 Gly Ala Ala Arg His Pro Thr Asn Leu AlaGln Val Lys Gln Phe Leu 20 25 30 caa ggg aaa gaa gaa acg cca gcc tca ttctta gaa aga tta aaa gag 144 Gln Gly Lys Glu Glu Thr Pro Ala Ser Phe LeuGlu Arg Leu Lys Glu 35 40 45 gct tac cga atg tat act ccc tat gac cct gaggac cca ggg cag gct 192 Ala Tyr Arg Met Tyr Thr Pro Tyr Asp Pro Glu AspPro Gly Gln Ala 50 55 60 gct agt gtt atc ctg tcc ttt atc tac cag tct agcccg gac ata aga 240 Ala Ser Val Ile Leu Ser Phe Ile Tyr Gln Ser Ser ProAsp Ile Arg 65 70 75 80 aat aag tta caa agg cta gaa ggc cta cag ggg ttcaca ctg tct gat 288 Asn Lys Leu Gln Arg Leu Glu Gly Leu Gln Gly Phe ThrLeu Ser Asp 85 90 95 ttg cta aaa gag gca gaa aag ata tac aac aaa agg gagacc cca gag 336 Leu Leu Lys Glu Ala Glu Lys Ile Tyr Asn Lys Arg Glu ThrPro Glu 100 105 110 gaa agg gaa gaa aga tta tgg cag cgg cag gaa gaa agagat aaa aag 384 Glu Arg Glu Glu Arg Leu Trp Gln Arg Gln Glu Glu Arg AspLys Lys 115 120 125 cgc cat aag gag atg act aaa gtt ctg gcc aca gta gttgct cag aat 432 Arg His Lys Glu Met Thr Lys Val Leu Ala Thr Val Val AlaGln Asn 130 135 140 aga gat aag gat aga gag gaa agt aaa ctg gga gat caaaga aaa ata 480 Arg Asp Lys Asp Arg Glu Glu Ser Lys Leu Gly Asp Gln ArgLys Ile 145 150 155 160 cct ctg ggg aaa gac cag tgt gcc tat tgc aag gaaaag gga cat tgg 528 Pro Leu Gly Lys Asp Gln Cys Ala Tyr Cys Lys Glu LysGly His Trp 165 170 175 gtt cgc gat tgc ccc aac cgg ccc cgg aag aaa cccgcc aac tcc act 576 Val Arg Asp Cys Pro Asn Arg Pro Arg Lys Lys Pro AlaAsn Ser Thr 180 185 190 ctc ctc aac tta gaa gat atg gcc aat cct agt ccaccc caa atg tat 624 Leu Leu Asn Leu Glu Asp Met Ala Asn Pro Ser Pro ProGln Met Tyr 195 200 205 aat gta act tgg gta ata acc aat gta caa acc aacacc caa gct aat 672 Asn Val Thr Trp Val Ile Thr Asn Val Gln Thr Asn ThrGln Ala Asn 210 215 220 gcc acc tct atg tta gga acc tta acc gat gtc taccct acc cta cat 720 Ala Thr Ser Met Leu Gly Thr Leu Thr Asp Val Tyr ProThr Leu His 225 230 235 240 gtt gac tta tgt gac cta gtg gga gac acc tgggaa cct atg gtc cta 768 Val Asp Leu Cys Asp Leu Val Gly Asp Thr Trp GluPro Met Val Leu 245 250 255 agc cca acc ggg tac cct ccc tca aaa tat ggatgt aaa act aca gat 816 Ser Pro Thr Gly Tyr Pro Pro Ser Lys Tyr Gly CysLys Thr Thr Asp 260 265 270 aga aaa aaa cag caa cag aca tac ccc ttt tacgtc tgc ccc ggg cat 864 Arg Lys Lys Gln Gln Gln Thr Tyr Pro Phe Tyr ValCys Pro Gly His 275 280 285 cgc ccc tcg ctg ggg cca aag gga aca cat tgtgga ggg gca caa gat 912 Arg Pro Ser Leu Gly Pro Lys Gly Thr His Cys GlyGly Ala Gln Asp 290 295 300 ggg ttt tgt gcc gca tgg gga tgt gaa acc accgga gaa gct tgg tgg 960 Gly Phe Cys Ala Ala Trp Gly Cys Glu Thr Thr GlyGlu Ala Trp Trp 305 310 315 320 aag ccc tcc tcc tca tgg gac tat atc acagta aaa aga ggg agt agt 1008 Lys Pro Ser Ser Ser Trp Asp Tyr Ile Thr ValLys Arg Gly Ser Ser 325 330 335 cag aac aat aac tgt gag gga aaa tgc aacccc ctg att ttg cag ttc 1056 Gln Asn Asn Asn Cys Glu Gly Lys Cys Asn ProLeu Ile Leu Gln Phe 340 345 350 acc cag aag ggg aaa caa gcc tct tgg gacgga cct aag atg tgg gga 1104 Thr Gln Lys Gly Lys Gln Ala Ser Trp Asp GlyPro Lys Met Trp Gly 355 360 365 ttg cgg cta tac cgt aca gga tat gac cctatc gcc tta ttc acg gta 1152 Leu Arg Leu Tyr Arg Thr Gly Tyr Asp Pro IleAla Leu Phe Thr Val 370 375 380 tcc cgg cgg gtg tca acc att acg ccg cctcag gca atg gga cca gac 1200 Ser Arg Arg Val Ser Thr Ile Thr Pro Pro GlnAla Met Gly Pro Asp 385 390 395 400 cta gtc tta cct gat caa aaa ccc ccatcc cga caa tct caa aca ggg 1248 Leu Val Leu Pro Asp Gln Lys Pro Pro SerArg Gln Ser Gln Thr Gly 405 410 415 tcc aaa gtg gcg acc cag agg ccc caaacg aat gaa agc gcc cca agg 1296 Ser Lys Val Ala Thr Gln Arg Pro Gln ThrAsn Glu Ser Ala Pro Arg 420 425 430 tct gtt gcc ccc acc acc gtg ggt cccaaa cgg att ggg acc gga gat 1344 Ser Val Ala Pro Thr Thr Val Gly Pro LysArg Ile Gly Thr Gly Asp 435 440 445 agg tta ata aat tta gta caa ggg gcatac cta gcc tta aat gcc acc 1392 Arg Leu Ile Asn Leu Val Gln Gly Ala TyrLeu Ala Leu Asn Ala Thr 450 455 460 gac ccc aac aaa act aaa gac tgt tggctc tgc ctg gtt tct cga cca 1440 Asp Pro Asn Lys Thr Lys Asp Cys Trp LeuCys Leu Val Ser Arg Pro 465 470 475 480 ccc tat tac gaa ggg att gca atctta ggt aac tac agc aac caa aca 1488 Pro Tyr Tyr Glu Gly Ile Ala Ile LeuGly Asn Tyr Ser Asn Gln Thr 485 490 495 aac cct ccc cca tcc tgc cta tctatt ccg cca cac aag ctg acc ata 1536 Asn Pro Pro Pro Ser Cys Leu Ser IlePro Pro His Lys Leu Thr Ile 500 505 510 tct aaa gta tca ggg caa gga ctgtgc ata ggg act gtt cct aag acc 1584 Ser Lys Val Ser Gly Gln Gly Leu CysIle Gly Thr Val Pro Lys Thr 515 520 525 cac cag gct ttg tgc aat aag acgcac cag gga cat aca ggg gcg gac 1632 His Gln Ala Leu Cys Asn Lys Thr HisGln Gly His Thr Gly Ala Asp 530 535 540 tat cga gcc gcc ccg cgg tat ctagcc gcc ccc aat ggc acc tat tgg 1680 Tyr Arg Ala Ala Pro Arg Tyr Leu AlaAla Pro Asn Gly Thr Tyr Trp 545 550 555 560 gcc tgt aac act gga ctc acccca tgc att tcc atg gcg gtg ctc aat 1728 Ala Cys Asn Thr Gly Leu Thr ProCys Ile Ser Met Ala Val Leu Asn 565 570 575 ttg acc tct gat ttt tgt gtctta atc gaa tta tgg ccc aga gtg act 1776 Leu Thr Ser Asp Phe Cys Val LeuIle Glu Leu Trp Pro Arg Val Thr 580 585 590 tac cat caa ccc gaa tat gtgtac aca cat ttt gcc aaa gct ggc agg 1824 Tyr His Gln Pro Glu Tyr Val TyrThr His Phe Ala Lys Ala Gly Arg 595 600 605 ttc cga aga 1833 Phe Arg Arg610 32 611 PRT Feline leukemia virus 32 Met Glu His Leu Arg Leu Tyr ArgGln Leu Leu Leu Ala Gly Leu Arg 1 5 10 15 Gly Ala Ala Arg His Pro ThrAsn Leu Ala Gln Val Lys Gln Phe Leu 20 25 30 Gln Gly Lys Glu Glu Thr ProAla Ser Phe Leu Glu Arg Leu Lys Glu 35 40 45 Ala Tyr Arg Met Tyr Thr ProTyr Asp Pro Glu Asp Pro Gly Gln Ala 50 55 60 Ala Ser Val Ile Leu Ser PheIle Tyr Gln Ser Ser Pro Asp Ile Arg 65 70 75 80 Asn Lys Leu Gln Arg LeuGlu Gly Leu Gln Gly Phe Thr Leu Ser Asp 85 90 95 Leu Leu Lys Glu Ala GluLys Ile Tyr Asn Lys Arg Glu Thr Pro Glu 100 105 110 Glu Arg Glu Glu ArgLeu Trp Gln Arg Gln Glu Glu Arg Asp Lys Lys 115 120 125 Arg His Lys GluMet Thr Lys Val Leu Ala Thr Val Val Ala Gln Asn 130 135 140 Arg Asp LysAsp Arg Glu Glu Ser Lys Leu Gly Asp Gln Arg Lys Ile 145 150 155 160 ProLeu Gly Lys Asp Gln Cys Ala Tyr Cys Lys Glu Lys Gly His Trp 165 170 175Val Arg Asp Cys Pro Asn Arg Pro Arg Lys Lys Pro Ala Asn Ser Thr 180 185190 Leu Leu Asn Leu Glu Asp Met Ala Asn Pro Ser Pro Pro Gln Met Tyr 195200 205 Asn Val Thr Trp Val Ile Thr Asn Val Gln Thr Asn Thr Gln Ala Asn210 215 220 Ala Thr Ser Met Leu Gly Thr Leu Thr Asp Val Tyr Pro Thr LeuHis 225 230 235 240 Val Asp Leu Cys Asp Leu Val Gly Asp Thr Trp Glu ProMet Val Leu 245 250 255 Ser Pro Thr Gly Tyr Pro Pro Ser Lys Tyr Gly CysLys Thr Thr Asp 260 265 270 Arg Lys Lys Gln Gln Gln Thr Tyr Pro Phe TyrVal Cys Pro Gly His 275 280 285 Arg Pro Ser Leu Gly Pro Lys Gly Thr HisCys Gly Gly Ala Gln Asp 290 295 300 Gly Phe Cys Ala Ala Trp Gly Cys GluThr Thr Gly Glu Ala Trp Trp 305 310 315 320 Lys Pro Ser Ser Ser Trp AspTyr Ile Thr Val Lys Arg Gly Ser Ser 325 330 335 Gln Asn Asn Asn Cys GluGly Lys Cys Asn Pro Leu Ile Leu Gln Phe 340 345 350 Thr Gln Lys Gly LysGln Ala Ser Trp Asp Gly Pro Lys Met Trp Gly 355 360 365 Leu Arg Leu TyrArg Thr Gly Tyr Asp Pro Ile Ala Leu Phe Thr Val 370 375 380 Ser Arg ArgVal Ser Thr Ile Thr Pro Pro Gln Ala Met Gly Pro Asp 385 390 395 400 LeuVal Leu Pro Asp Gln Lys Pro Pro Ser Arg Gln Ser Gln Thr Gly 405 410 415Ser Lys Val Ala Thr Gln Arg Pro Gln Thr Asn Glu Ser Ala Pro Arg 420 425430 Ser Val Ala Pro Thr Thr Val Gly Pro Lys Arg Ile Gly Thr Gly Asp 435440 445 Arg Leu Ile Asn Leu Val Gln Gly Ala Tyr Leu Ala Leu Asn Ala Thr450 455 460 Asp Pro Asn Lys Thr Lys Asp Cys Trp Leu Cys Leu Val Ser ArgPro 465 470 475 480 Pro Tyr Tyr Glu Gly Ile Ala Ile Leu Gly Asn Tyr SerAsn Gln Thr 485 490 495 Asn Pro Pro Pro Ser Cys Leu Ser Ile Pro Pro HisLys Leu Thr Ile 500 505 510 Ser Lys Val Ser Gly Gln Gly Leu Cys Ile GlyThr Val Pro Lys Thr 515 520 525 His Gln Ala Leu Cys Asn Lys Thr His GlnGly His Thr Gly Ala Asp 530 535 540 Tyr Arg Ala Ala Pro Arg Tyr Leu AlaAla Pro Asn Gly Thr Tyr Trp 545 550 555 560 Ala Cys Asn Thr Gly Leu ThrPro Cys Ile Ser Met Ala Val Leu Asn 565 570 575 Leu Thr Ser Asp Phe CysVal Leu Ile Glu Leu Trp Pro Arg Val Thr 580 585 590 Tyr His Gln Pro GluTyr Val Tyr Thr His Phe Ala Lys Ala Gly Arg 595 600 605 Phe Arg Arg 61033 1812 DNA canine distemper virus CDS (1)..(1812) 33 atg ctc ccc taccaa gac aag gtg ggt gcc ttc tac aag gat aat gca 48 Met Leu Pro Tyr GlnAsp Lys Val Gly Ala Phe Tyr Lys Asp Asn Ala 1 5 10 15 aga gcc aat tcaacc aag ctg tcc tta gtg aca gaa gga cat ggg ggc 96 Arg Ala Asn Ser ThrLys Leu Ser Leu Val Thr Glu Gly His Gly Gly 20 25 30 agg aga cca cct tatttg ttg ttt gtc ctt ctc atc tta ttg gtt ggt 144 Arg Arg Pro Pro Tyr LeuLeu Phe Val Leu Leu Ile Leu Leu Val Gly 35 40 45 atc ctg gcc ttg ctt gctatc act gga gtt cga ttt cac caa gta tca 192 Ile Leu Ala Leu Leu Ala IleThr Gly Val Arg Phe His Gln Val Ser 50 55 60 act agt aat atg gaa ttt agcaga ttg ctg aaa gag gat atg gag aaa 240 Thr Ser Asn Met Glu Phe Ser ArgLeu Leu Lys Glu Asp Met Glu Lys 65 70 75 80 tca gag gcc gta cat cac caagtc ata gat gtc ttg aca ccg ctc ttc 288 Ser Glu Ala Val His His Gln ValIle Asp Val Leu Thr Pro Leu Phe 85 90 95 aag att att gga gat gag att gggtta cgg ttg cca caa aag cta aac 336 Lys Ile Ile Gly Asp Glu Ile Gly LeuArg Leu Pro Gln Lys Leu Asn 100 105 110 gag atc aaa caa ttt atc ctt caaaag aca aat ttc ttc aat ccg aac 384 Glu Ile Lys Gln Phe Ile Leu Gln LysThr Asn Phe Phe Asn Pro Asn 115 120 125 aga gaa ttc gac ttc cgc gat ctccac tgg tgc att aac ccg cct agt 432 Arg Glu Phe Asp Phe Arg Asp Leu HisTrp Cys Ile Asn Pro Pro Ser 130 135 140 acg gtc aag gtg aat ttt act aattac tgt gag tca att ggg atc aga 480 Thr Val Lys Val Asn Phe Thr Asn TyrCys Glu Ser Ile Gly Ile Arg 145 150 155 160 aaa gct att gca tcg gca gcaaat cct atc ctt tta tca gcc cta tct 528 Lys Ala Ile Ala Ser Ala Ala AsnPro Ile Leu Leu Ser Ala Leu Ser 165 170 175 ggg ggc aga ggt gac ata ttccca cca cac aga tgc agt gga gct act 576 Gly Gly Arg Gly Asp Ile Phe ProPro His Arg Cys Ser Gly Ala Thr 180 185 190 act tca gta ggc aaa gtt ttcccc cta tca gtc tca tta tcc atg tct 624 Thr Ser Val Gly Lys Val Phe ProLeu Ser Val Ser Leu Ser Met Ser 195 200 205 ttg atc tca aga acc tca gaggta atc aat atg ctg acc gct atc tca 672 Leu Ile Ser Arg Thr Ser Glu ValIle Asn Met Leu Thr Ala Ile Ser 210 215 220 gac ggc gtg tat ggc aaa acttac ttg cta gtg cct gat gat ata gaa 720 Asp Gly Val Tyr Gly Lys Thr TyrLeu Leu Val Pro Asp Asp Ile Glu 225 230 235 240 aga gag ttc gac act cgagag att cga gtc ttt gaa ata ggg ttc atc 768 Arg Glu Phe Asp Thr Arg GluIle Arg Val Phe Glu Ile Gly Phe Ile 245 250 255 aaa agg tgg ctg aat gacatg cca tta ctc caa aca acc aac tat atg 816 Lys Arg Trp Leu Asn Asp MetPro Leu Leu Gln Thr Thr Asn Tyr Met 260 265 270 gta ctc ccg aag aat tccaaa gcc aag gta tgt act ata gca gtg ggt 864 Val Leu Pro Lys Asn Ser LysAla Lys Val Cys Thr Ile Ala Val Gly 275 280 285 gag ttg aca ctg gct tccttg tgt gta gaa gag agc act gta tta tta 912 Glu Leu Thr Leu Ala Ser LeuCys Val Glu Glu Ser Thr Val Leu Leu 290 295 300 tat cat gac agc agt ggttca caa gat ggt att cta gta gtg aca ctg 960 Tyr His Asp Ser Ser Gly SerGln Asp Gly Ile Leu Val Val Thr Leu 305 310 315 320 ggg ata ttt tgg gcaaca cct atg gat cac att gag gaa gtg ata cct 1008 Gly Ile Phe Trp Ala ThrPro Met Asp His Ile Glu Glu Val Ile Pro 325 330 335 gtc gct cac cca tcaatg aag aaa ata cat ata aca aac cac cgt ggt 1056 Val Ala His Pro Ser MetLys Lys Ile His Ile Thr Asn His Arg Gly 340 345 350 ttt ata aaa gat tcaatt gca acc tgg atg gtg cct gcc ctg gcc tct 1104 Phe Ile Lys Asp Ser IleAla Thr Trp Met Val Pro Ala Leu Ala Ser 355 360 365 gag aaa caa gaa gaacaa aaa ggt tgt ctg gag tca gct tgt caa aga 1152 Glu Lys Gln Glu Glu GlnLys Gly Cys Leu Glu Ser Ala Cys Gln Arg 370 375 380 aaa acc tac ccc atgtgc aac caa gcg tca tgg gaa ccc ttc gga gga 1200 Lys Thr Tyr Pro Met CysAsn Gln Ala Ser Trp Glu Pro Phe Gly Gly 385 390 395 400 aga cag ttg ccatct tat ggg cgg ttg aca tta cct cta gat gca agt 1248 Arg Gln Leu Pro SerTyr Gly Arg Leu Thr Leu Pro Leu Asp Ala Ser 405 410 415 gtt gac ctt caactt aac ata tcg ttc aca tac ggt ccg gtt ata ctg 1296 Val Asp Leu Gln LeuAsn Ile Ser Phe Thr Tyr Gly Pro Val Ile Leu 420 425 430 aat gga gat ggtatg gat tat tat gaa agc cca ctt ttg aac tcc gga 1344 Asn Gly Asp Gly MetAsp Tyr Tyr Glu Ser Pro Leu Leu Asn Ser Gly 435 440 445 tgg ctt acc attccc ccc aaa gac gga aca atc tct gga ttg ata aac 1392 Trp Leu Thr Ile ProPro Lys Asp Gly Thr Ile Ser Gly Leu Ile Asn 450 455 460 aaa gca ggt agagga gac cag ttc act gta ctc ccc cat gtg tta aca 1440 Lys Ala Gly Arg GlyAsp Gln Phe Thr Val Leu Pro His Val Leu Thr 465 470 475 480 ttt gcg cccagg gaa tca agt gga aat tgt tat tta cct att caa aca 1488 Phe Ala Pro ArgGlu Ser Ser Gly Asn Cys Tyr Leu Pro Ile Gln Thr 485 490 495 tct caa attaga gat aga gat gtc ctc att gag tcc aat ata gtg gtg 1536 Ser Gln Ile ArgAsp Arg Asp Val Leu Ile Glu Ser Asn Ile Val Val 500 505 510 ttg cct acacag agt att aga tat gtc ata gca acg tat gac ata tca 1584 Leu Pro Thr GlnSer Ile Arg Tyr Val Ile Ala Thr Tyr Asp Ile Ser 515 520 525 cga agt gatcat gct att gtt tat tat gtt tat gac cca atc cgg acg 1632 Arg Ser Asp HisAla Ile Val Tyr Tyr Val Tyr Asp Pro Ile Arg Thr 530 535 540 att tct tatacg cac cca ttt aga cta act acc aag ggt aga cct gat 1680 Ile Ser Tyr ThrHis Pro Phe Arg Leu Thr Thr Lys Gly Arg Pro Asp 545 550 555 560 ttc ctaagg att gaa tgt ttt gtg tgg gat gac aat ttg tgg tgt cac 1728 Phe Leu ArgIle Glu Cys Phe Val Trp Asp Asp Asn Leu Trp Cys His 565 570 575 caa ttttac aga ttc gag gct gac atc gcc aac tct aca acc agt gtt 1776 Gln Phe TyrArg Phe Glu Ala Asp Ile Ala Asn Ser Thr Thr Ser Val 580 585 590 gag aattta gtc cgt ata aga ttc tca tgt aac cgt 1812 Glu Asn Leu Val Arg Ile ArgPhe Ser Cys Asn Arg 595 600 34 604 PRT canine distemper virus 34 Met LeuPro Tyr Gln Asp Lys Val Gly Ala Phe Tyr Lys Asp Asn Ala 1 5 10 15 ArgAla Asn Ser Thr Lys Leu Ser Leu Val Thr Glu Gly His Gly Gly 20 25 30 ArgArg Pro Pro Tyr Leu Leu Phe Val Leu Leu Ile Leu Leu Val Gly 35 40 45 IleLeu Ala Leu Leu Ala Ile Thr Gly Val Arg Phe His Gln Val Ser 50 55 60 ThrSer Asn Met Glu Phe Ser Arg Leu Leu Lys Glu Asp Met Glu Lys 65 70 75 80Ser Glu Ala Val His His Gln Val Ile Asp Val Leu Thr Pro Leu Phe 85 90 95Lys Ile Ile Gly Asp Glu Ile Gly Leu Arg Leu Pro Gln Lys Leu Asn 100 105110 Glu Ile Lys Gln Phe Ile Leu Gln Lys Thr Asn Phe Phe Asn Pro Asn 115120 125 Arg Glu Phe Asp Phe Arg Asp Leu His Trp Cys Ile Asn Pro Pro Ser130 135 140 Thr Val Lys Val Asn Phe Thr Asn Tyr Cys Glu Ser Ile Gly IleArg 145 150 155 160 Lys Ala Ile Ala Ser Ala Ala Asn Pro Ile Leu Leu SerAla Leu Ser 165 170 175 Gly Gly Arg Gly Asp Ile Phe Pro Pro His Arg CysSer Gly Ala Thr 180 185 190 Thr Ser Val Gly Lys Val Phe Pro Leu Ser ValSer Leu Ser Met Ser 195 200 205 Leu Ile Ser Arg Thr Ser Glu Val Ile AsnMet Leu Thr Ala Ile Ser 210 215 220 Asp Gly Val Tyr Gly Lys Thr Tyr LeuLeu Val Pro Asp Asp Ile Glu 225 230 235 240 Arg Glu Phe Asp Thr Arg GluIle Arg Val Phe Glu Ile Gly Phe Ile 245 250 255 Lys Arg Trp Leu Asn AspMet Pro Leu Leu Gln Thr Thr Asn Tyr Met 260 265 270 Val Leu Pro Lys AsnSer Lys Ala Lys Val Cys Thr Ile Ala Val Gly 275 280 285 Glu Leu Thr LeuAla Ser Leu Cys Val Glu Glu Ser Thr Val Leu Leu 290 295 300 Tyr His AspSer Ser Gly Ser Gln Asp Gly Ile Leu Val Val Thr Leu 305 310 315 320 GlyIle Phe Trp Ala Thr Pro Met Asp His Ile Glu Glu Val Ile Pro 325 330 335Val Ala His Pro Ser Met Lys Lys Ile His Ile Thr Asn His Arg Gly 340 345350 Phe Ile Lys Asp Ser Ile Ala Thr Trp Met Val Pro Ala Leu Ala Ser 355360 365 Glu Lys Gln Glu Glu Gln Lys Gly Cys Leu Glu Ser Ala Cys Gln Arg370 375 380 Lys Thr Tyr Pro Met Cys Asn Gln Ala Ser Trp Glu Pro Phe GlyGly 385 390 395 400 Arg Gln Leu Pro Ser Tyr Gly Arg Leu Thr Leu Pro LeuAsp Ala Ser 405 410 415 Val Asp Leu Gln Leu Asn Ile Ser Phe Thr Tyr GlyPro Val Ile Leu 420 425 430 Asn Gly Asp Gly Met Asp Tyr Tyr Glu Ser ProLeu Leu Asn Ser Gly 435 440 445 Trp Leu Thr Ile Pro Pro Lys Asp Gly ThrIle Ser Gly Leu Ile Asn 450 455 460 Lys Ala Gly Arg Gly Asp Gln Phe ThrVal Leu Pro His Val Leu Thr 465 470 475 480 Phe Ala Pro Arg Glu Ser SerGly Asn Cys Tyr Leu Pro Ile Gln Thr 485 490 495 Ser Gln Ile Arg Asp ArgAsp Val Leu Ile Glu Ser Asn Ile Val Val 500 505 510 Leu Pro Thr Gln SerIle Arg Tyr Val Ile Ala Thr Tyr Asp Ile Ser 515 520 525 Arg Ser Asp HisAla Ile Val Tyr Tyr Val Tyr Asp Pro Ile Arg Thr 530 535 540 Ile Ser TyrThr His Pro Phe Arg Leu Thr Thr Lys Gly Arg Pro Asp 545 550 555 560 PheLeu Arg Ile Glu Cys Phe Val Trp Asp Asp Asn Leu Trp Cys His 565 570 575Gln Phe Tyr Arg Phe Glu Ala Asp Ile Ala Asn Ser Thr Thr Ser Val 580 585590 Glu Asn Leu Val Arg Ile Arg Phe Ser Cys Asn Arg 595 600 35 1986 DNAcanine distemper virus CDS (1)..(1986) 35 atg cac agg gga atc ccc aaaagc tcc aaa acc caa aca cat acc caa 48 Met His Arg Gly Ile Pro Lys SerSer Lys Thr Gln Thr His Thr Gln 1 5 10 15 caa gac cgc ccc cca caa cccagc acc gaa ctc gaa gag acc agg acc 96 Gln Asp Arg Pro Pro Gln Pro SerThr Glu Leu Glu Glu Thr Arg Thr 20 25 30 tcc cga gca cga cac agc aca acatca gct cag cga tcc acg cac tac 144 Ser Arg Ala Arg His Ser Thr Thr SerAla Gln Arg Ser Thr His Tyr 35 40 45 gat cct cga aca tcg gac aga ccc gtctcc tac acc atg aac agg acc 192 Asp Pro Arg Thr Ser Asp Arg Pro Val SerTyr Thr Met Asn Arg Thr 50 55 60 agg tcc cgc aag caa acc agc cac aga ttgaag aac atc cca gtt cac 240 Arg Ser Arg Lys Gln Thr Ser His Arg Leu LysAsn Ile Pro Val His 65 70 75 80 gga aac cac gag gcc acc atc cag cac atacca gag agt gtc tca aaa 288 Gly Asn His Glu Ala Thr Ile Gln His Ile ProGlu Ser Val Ser Lys 85 90 95 gga gcg aga tcc cag atc gaa agg cgg caa cccaat gca atc aac tca 336 Gly Ala Arg Ser Gln Ile Glu Arg Arg Gln Pro AsnAla Ile Asn Ser 100 105 110 ggc tct cat tgc acc tgg tta gtc ctg tgg tgcctc gga atg gcc agt 384 Gly Ser His Cys Thr Trp Leu Val Leu Trp Cys LeuGly Met Ala Ser 115 120 125 ctc ttt ctt tgt tcc aag gct cag ata cat tgggat aat ttg tca act 432 Leu Phe Leu Cys Ser Lys Ala Gln Ile His Trp AspAsn Leu Ser Thr 130 135 140 att ggg att atc ggg act gat aat gtc cat tacaag atc atg act agg 480 Ile Gly Ile Ile Gly Thr Asp Asn Val His Tyr LysIle Met Thr Arg 145 150 155 160 ccc agt cac cag tac ttg gtc ata aaa ttgatc cct aat gct tca ctt 528 Pro Ser His Gln Tyr Leu Val Ile Lys Leu IlePro Asn Ala Ser Leu 165 170 175 ata gag aat tgt acc aaa gca gaa tta ggtgag tat gag aaa tta ttg 576 Ile Glu Asn Cys Thr Lys Ala Glu Leu Gly GluTyr Glu Lys Leu Leu 180 185 190 aat tca gtc ctc gaa cca atc aac caa gctttg act cta atg acc aag 624 Asn Ser Val Leu Glu Pro Ile Asn Gln Ala LeuThr Leu Met Thr Lys 195 200 205 aat gtg aag ccc ctg cag tca tta ggg tcaggt agg aga caa agg cgt 672 Asn Val Lys Pro Leu Gln Ser Leu Gly Ser GlyArg Arg Gln Arg Arg 210 215 220 ttt gca gga gtg gta ctt gca ggt gta gcttta gga gtg gct aca gct 720 Phe Ala Gly Val Val Leu Ala Gly Val Ala LeuGly Val Ala Thr Ala 225 230 235 240 gca caa atc act gca gga ata gct ttacat caa tcc aac ctc aat gct 768 Ala Gln Ile Thr Ala Gly Ile Ala Leu HisGln Ser Asn Leu Asn Ala 245 250 255 caa gca atc caa tct ctt aga acc agcctt gaa cag tct aac aaa gct 816 Gln Ala Ile Gln Ser Leu Arg Thr Ser LeuGlu Gln Ser Asn Lys Ala 260 265 270 ata gaa gaa att agg gag gct acc caagaa acc gtc att gcc gtt cag 864 Ile Glu Glu Ile Arg Glu Ala Thr Gln GluThr Val Ile Ala Val Gln 275 280 285 gga gtc cag gac tac gtc aac aac gaactc gtc cct gcc atg caa cat 912 Gly Val Gln Asp Tyr Val Asn Asn Glu LeuVal Pro Ala Met Gln His 290 295 300 atg tca tgt gaa tta gtt ggg cag agatta ggg tta aga ctg ctt cgg 960 Met Ser Cys Glu Leu Val Gly Gln Arg LeuGly Leu Arg Leu Leu Arg 305 310 315 320 tat tat act gag ttg ttg tca atattt ggc ccg agt tta cgt gac cct 1008 Tyr Tyr Thr Glu Leu Leu Ser Ile PheGly Pro Ser Leu Arg Asp Pro 325 330 335 att tca gcc gag ata tca att caggca ctg att tat gct ctt gga gga 1056 Ile Ser Ala Glu Ile Ser Ile Gln AlaLeu Ile Tyr Ala Leu Gly Gly 340 345 350 gaa att cat aag ata ctt gag aagttg gga tat tct gga agt gat atg 1104 Glu Ile His Lys Ile Leu Glu Lys LeuGly Tyr Ser Gly Ser Asp Met 355 360 365 att gca atc ttg gag agt cgg gggata aaa aca aaa ata act cat gtt 1152 Ile Ala Ile Leu Glu Ser Arg Gly IleLys Thr Lys Ile Thr His Val 370 375 380 gat ctt ccc ggg aaa ttc atc atccta agt atc tca tac cca act tta 1200 Asp Leu Pro Gly Lys Phe Ile Ile LeuSer Ile Ser Tyr Pro Thr Leu 385 390 395 400 tca gaa gtc aag ggg gtt atagtc cac aga ctg gaa gca gtt tct tac 1248 Ser Glu Val Lys Gly Val Ile ValHis Arg Leu Glu Ala Val Ser Tyr 405 410 415 aac ata gga tca caa gag tggtac acc act gtc ccg agg tat att gca 1296 Asn Ile Gly Ser Gln Glu Trp TyrThr Thr Val Pro Arg Tyr Ile Ala 420 425 430 act aat ggt tac tta ata tctaat ttt gat gag tca tct tgt gta ttc 1344 Thr Asn Gly Tyr Leu Ile Ser AsnPhe Asp Glu Ser Ser Cys Val Phe 435 440 445 gtc tca gag tca gcc att tgtagc cag aac tcc ctg tat ccc atg agc 1392 Val Ser Glu Ser Ala Ile Cys SerGln Asn Ser Leu Tyr Pro Met Ser 450 455 460 cca ctc tta caa caa tgt attagg ggc gac act tca tct tgt gct cgg 1440 Pro Leu Leu Gln Gln Cys Ile ArgGly Asp Thr Ser Ser Cys Ala Arg 465 470 475 480 acc ttg gta tct ggg actatg ggc aac aaa ttt att ctg tca aaa ggt 1488 Thr Leu Val Ser Gly Thr MetGly Asn Lys Phe Ile Leu Ser Lys Gly 485 490 495 aat atc gtc gca aat tgtgct tct ata cta tgt aag tgt tat agc aca 1536 Asn Ile Val Ala Asn Cys AlaSer Ile Leu Cys Lys Cys Tyr Ser Thr 500 505 510 agc aca att att aat cagagt cct gat aag ttg ctg aca ttc att gcc 1584 Ser Thr Ile Ile Asn Gln SerPro Asp Lys Leu Leu Thr Phe Ile Ala 515 520 525 tcc gat acc tgc cca ctggtt gaa ata gat ggt gct act atc caa gtt 1632 Ser Asp Thr Cys Pro Leu ValGlu Ile Asp Gly Ala Thr Ile Gln Val 530 535 540 gga ggc agg caa tac cctgat atg gta tac gaa ggc aaa gtt gcc tta 1680 Gly Gly Arg Gln Tyr Pro AspMet Val Tyr Glu Gly Lys Val Ala Leu 545 550 555 560 ggc cct gct ata tcactt gat agg tta gat gta ggt aca aac tta ggg 1728 Gly Pro Ala Ile Ser LeuAsp Arg Leu Asp Val Gly Thr Asn Leu Gly 565 570 575 aac gcc ctt aag aaactg gat gat gct aag gta ctg ata gac tcc tct 1776 Asn Ala Leu Lys Lys LeuAsp Asp Ala Lys Val Leu Ile Asp Ser Ser 580 585 590 aac cag atc ctt gagacg gtt agg cgc tct tcc ttt aat ttt ggc agt 1824 Asn Gln Ile Leu Glu ThrVal Arg Arg Ser Ser Phe Asn Phe Gly Ser 595 600 605 ctc ctc agc gtt cctata tta agt tgt aca gcc ctg gct ttg ttg ttg 1872 Leu Leu Ser Val Pro IleLeu Ser Cys Thr Ala Leu Ala Leu Leu Leu 610 615 620 ctg att tac tgt tgtaaa aga cgc tac caa cag aca ctc aag cag cat 1920 Leu Ile Tyr Cys Cys LysArg Arg Tyr Gln Gln Thr Leu Lys Gln His 625 630 635 640 act aag gtc gatccg gca ttt aaa cct gat cta act gga act tcg aaa 1968 Thr Lys Val Asp ProAla Phe Lys Pro Asp Leu Thr Gly Thr Ser Lys 645 650 655 tcc tat gtg agatca ctc 1986 Ser Tyr Val Arg Ser Leu 660 36 662 PRT canine distempervirus 36 Met His Arg Gly Ile Pro Lys Ser Ser Lys Thr Gln Thr His Thr Gln1 5 10 15 Gln Asp Arg Pro Pro Gln Pro Ser Thr Glu Leu Glu Glu Thr ArgThr 20 25 30 Ser Arg Ala Arg His Ser Thr Thr Ser Ala Gln Arg Ser Thr HisTyr 35 40 45 Asp Pro Arg Thr Ser Asp Arg Pro Val Ser Tyr Thr Met Asn ArgThr 50 55 60 Arg Ser Arg Lys Gln Thr Ser His Arg Leu Lys Asn Ile Pro ValHis 65 70 75 80 Gly Asn His Glu Ala Thr Ile Gln His Ile Pro Glu Ser ValSer Lys 85 90 95 Gly Ala Arg Ser Gln Ile Glu Arg Arg Gln Pro Asn Ala IleAsn Ser 100 105 110 Gly Ser His Cys Thr Trp Leu Val Leu Trp Cys Leu GlyMet Ala Ser 115 120 125 Leu Phe Leu Cys Ser Lys Ala Gln Ile His Trp AspAsn Leu Ser Thr 130 135 140 Ile Gly Ile Ile Gly Thr Asp Asn Val His TyrLys Ile Met Thr Arg 145 150 155 160 Pro Ser His Gln Tyr Leu Val Ile LysLeu Ile Pro Asn Ala Ser Leu 165 170 175 Ile Glu Asn Cys Thr Lys Ala GluLeu Gly Glu Tyr Glu Lys Leu Leu 180 185 190 Asn Ser Val Leu Glu Pro IleAsn Gln Ala Leu Thr Leu Met Thr Lys 195 200 205 Asn Val Lys Pro Leu GlnSer Leu Gly Ser Gly Arg Arg Gln Arg Arg 210 215 220 Phe Ala Gly Val ValLeu Ala Gly Val Ala Leu Gly Val Ala Thr Ala 225 230 235 240 Ala Gln IleThr Ala Gly Ile Ala Leu His Gln Ser Asn Leu Asn Ala 245 250 255 Gln AlaIle Gln Ser Leu Arg Thr Ser Leu Glu Gln Ser Asn Lys Ala 260 265 270 IleGlu Glu Ile Arg Glu Ala Thr Gln Glu Thr Val Ile Ala Val Gln 275 280 285Gly Val Gln Asp Tyr Val Asn Asn Glu Leu Val Pro Ala Met Gln His 290 295300 Met Ser Cys Glu Leu Val Gly Gln Arg Leu Gly Leu Arg Leu Leu Arg 305310 315 320 Tyr Tyr Thr Glu Leu Leu Ser Ile Phe Gly Pro Ser Leu Arg AspPro 325 330 335 Ile Ser Ala Glu Ile Ser Ile Gln Ala Leu Ile Tyr Ala LeuGly Gly 340 345 350 Glu Ile His Lys Ile Leu Glu Lys Leu Gly Tyr Ser GlySer Asp Met 355 360 365 Ile Ala Ile Leu Glu Ser Arg Gly Ile Lys Thr LysIle Thr His Val 370 375 380 Asp Leu Pro Gly Lys Phe Ile Ile Leu Ser IleSer Tyr Pro Thr Leu 385 390 395 400 Ser Glu Val Lys Gly Val Ile Val HisArg Leu Glu Ala Val Ser Tyr 405 410 415 Asn Ile Gly Ser Gln Glu Trp TyrThr Thr Val Pro Arg Tyr Ile Ala 420 425 430 Thr Asn Gly Tyr Leu Ile SerAsn Phe Asp Glu Ser Ser Cys Val Phe 435 440 445 Val Ser Glu Ser Ala IleCys Ser Gln Asn Ser Leu Tyr Pro Met Ser 450 455 460 Pro Leu Leu Gln GlnCys Ile Arg Gly Asp Thr Ser Ser Cys Ala Arg 465 470 475 480 Thr Leu ValSer Gly Thr Met Gly Asn Lys Phe Ile Leu Ser Lys Gly 485 490 495 Asn IleVal Ala Asn Cys Ala Ser Ile Leu Cys Lys Cys Tyr Ser Thr 500 505 510 SerThr Ile Ile Asn Gln Ser Pro Asp Lys Leu Leu Thr Phe Ile Ala 515 520 525Ser Asp Thr Cys Pro Leu Val Glu Ile Asp Gly Ala Thr Ile Gln Val 530 535540 Gly Gly Arg Gln Tyr Pro Asp Met Val Tyr Glu Gly Lys Val Ala Leu 545550 555 560 Gly Pro Ala Ile Ser Leu Asp Arg Leu Asp Val Gly Thr Asn LeuGly 565 570 575 Asn Ala Leu Lys Lys Leu Asp Asp Ala Lys Val Leu Ile AspSer Ser 580 585 590 Asn Gln Ile Leu Glu Thr Val Arg Arg Ser Ser Phe AsnPhe Gly Ser 595 600 605 Leu Leu Ser Val Pro Ile Leu Ser Cys Thr Ala LeuAla Leu Leu Leu 610 615 620 Leu Ile Tyr Cys Cys Lys Arg Arg Tyr Gln GlnThr Leu Lys Gln His 625 630 635 640 Thr Lys Val Asp Pro Ala Phe Lys ProAsp Leu Thr Gly Thr Ser Lys 645 650 655 Ser Tyr Val Arg Ser Leu 660

What is claimed is:
 1. A method to determine the immune status of ananimal, said method comprising the steps of: (a) contacting a biologicalspecimen of said animal with a recombinant infectious agent antigen thatis specific for detecting an antibody selective for said infectiousagent, under conditions suitable for formation of a complex between saidrecombinant antigen and said antibody; and (b) detecting the presence orabsence of said complex, wherein presence or absence of said complex isindicative of the immune status of said animal.
 2. The method of claim1, wherein presence of said complex is indicative of non-susceptibilityto infection by said infectious agent.
 3. The method of claim 1, whereinsaid antibody is selected from the group consisting of amaternally-derived antibody, an antibody generated in response tonatural infection by said infectious agent and an antibody generated inresponse to vaccination against said infectious agent.
 4. The method ofclaim 1, wherein said biological specimen is selected from the groupconsisting of blood, serum, plasma, saliva, urine, tears, aqueous humor,cerebrospinal fluid, lymph, nasal secretion, tracheobronchial aspirate,milk, colostrum, intestinal secretion, and feces.
 5. The method of claim1, wherein said animal is selected from the group consisting of a cat,dog, and horse.
 6. The method of claim 1, wherein said recombinantantigen is immobilized on a substrate.
 7. The method of claim 1, whereinsaid method comprises performing an assay selected from the groupconsisting of an enzyme-linked immunoassay, a radioimmunoassay, afluorescence immunoassay, a luminescence assay, a phosphorescence assay,an immunoblot assay, an immunodot assay, an immunoprecipitation assay, alateral flow assay, a flow-through assay, an agglutination assay, aparticulate-based assay, and an electronic sensory assay.
 8. The methodof claim 1, wherein said step of detecting comprises applying adetection reagent that binds to said complex, if present, to obtain atest signal, wherein presence or absence of a test signal is indicativeof the immune status of said animal.
 9. The method of claim 8, whereinsaid detection reagent comprises an antibody-binding partner conjugatedto a detectable marker.
 10. The method of claim 9, wherein saidantibody-binding partner is selected from the group consisting of anFc-binding antibody, an Fc receptor, and an antibody-binding bacterialsurface protein.
 11. The method of claim 9, wherein said detectablemarker is selected from the group consisting of an enzyme, a radioactivelabel, a fluorescent label, a luminescent label, a phosphorescent label,a chromophoric label, a metal sol label, a metal-binding label, aphysical label, an electronic label, and a ligand.
 12. The method ofclaim 1, wherein said recombinant antigen further comprises a detectablemarker.
 13. The method of claim 1, wherein said method is conductedwithin about one day.
 14. The method of claim 1, wherein said method isconducted within about one hour.
 15. The method of claim 1, wherein saidmethod is conducted in a time period of between about one minute andabout fifteen minutes.
 16. The method of claim 1, wherein saidrecombinant antigen is selected from the group consisting of arecombinant viral antigen, a recombinant bacterial antigen, arecombinant fungal antigen, a recombinant endoparasite antigen, and arecombinant ectoparasite antigen.
 17. The method of claim 1, whereinsaid recombinant antigen is a recombinant viral antigen.
 18. The methodof claim 1, wherein said recombinant antigen is selected from the groupconsisting of a calicivirus protein, a distemper virus protein, aherpesvirus protein, a leukemia virus protein, and a parvovirus protein.19. The method of claim 1, wherein said recombinant antigen is selectedfrom the group consisting of a feline calicivirus capsid protein, afeline herpesvirus glycoprotein B protein, a feline herpesvirusglycoprotein C protein, a feline herpesvirus glycoprotein D protein, afeline parvovirus VP12 protein, a feline parvovirus VP2 protein, afeline leukemia virus p27 protein, a feline leukemia virus gp70 protein,a feline leukemia virus p27-gp70 fusion protein, a canine distempervirus fusion protein, and a canine distemper virus hemagglutininprotein.
 20. The method of claim 1, wherein said recombinant antigen isselected from the group consisting of PFCVCP₆₇₁, PFCVCP₅₄₇, PFPVVP2₅₈₄,PFPVVP2C₂₄₃, PFPVpVP2₁₆₂₀, PFPVpVP2₄₇₇, PFHVgB₉₄₃, PFHVgB₂₅₀, PFHVgC₅₃₄,PFHVgC₄₆₇, PFHVgC_(467(opt)), PFHVgD₃₇₄, PFHVgD₃00, PFeLVp27₂₅₃,PFeLVp27₆,₉, PFeLVp27-gp70₆,₁, PCDVH₆₀₄, PCDVF₆₆₂, PHis-PFCVCP₆₇₁,PHis-PFCVCP₅₄₇, PHis-PFPVVP2₅₈₄, PHis-PFPVVP2C₂₄₃, PHis-PFPVpVP12₆₂₀,PHis-PFPVpVP2₄₇₇, PHis-PFHVgB₉₄₃, PHis-PFHVgB₂₅₀, PHis-PFHVgC₅₃₄,PHis-PFHVgC₄₆₇, PHis-PFHVgC_(467(opt)), PHis-PFHVgD₃₇₄, PHis-PFHVgD₃₀₀,PHis-PFeLVp27₂₅₃, PHis-PFeLVp27₆₁₉, PHis-PFeLVp27-gp70₆₁₁,PHis-PCDVH₆₀₄, and PHis-PCDVF₆₆₂.
 21. The method of claim 1, whereinsaid recombinant antigen comprises an amino acid sequence selected fromthe group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ IDNO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ IDNO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ IDNO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34 and SEQ ID NO:36. 22.The method of claim 1, wherein said recombinant antigen is encoded by anucleic acid sequence selected from the group consisting of SEQ ID NO:1,SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ IDNO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ IDNO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ IDNO:33, and SEQ ID NO:35.
 23. The method of claim 1, wherein saidbiological specimen is contacted with a recombinant calicivirus antigen,a recombinant herpesvirus antigen and a recombinant parvovirus antigenunder conditions such that the immune status of said animal tocalicivirus, herpesvirus and parvovirus infection is determined.
 24. Amethod to determine whether to vaccinate an animal, said methodcomprising the steps of: (a) contacting a biological specimen of saidanimal with a recombinant infectious agent antigen that is specific fordetecting an antibody selective for said infectious agent, underconditions suitable for formation of a complex between said recombinantantigen and said antibody; and (b) detecting the presence or absence ofsaid complex, wherein presence of said complex indicates that saidanimal need not be vaccinated and wherein absence of said complexindicates that said animal should be vaccinated.
 25. The method of claim24, wherein said step of detecting comprises applying a detectionreagent that binds to said complex, if present, to obtain a test signal,wherein presence of said test signal indicates that said animal need notbe vaccinated and wherein absence of said test signal indicates thatsaid animal should be vaccinated.
 26. A recombinant antigen comprising arecombinant protein having an amino acid sequence selected from thegroup consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8,SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18,SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28,SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, and an aminoacid sequence encoded by an allelic variant of a nucleic acid sequenceencoding any of said amino acid sequences.
 27. The recombinant antigenof claim 26, wherein said recombinant antigen is encoded by a nucleicacid molecule comprising a nucleic acid sequence selected from the groupconsisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ IDNO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ IDNO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ IDNO:29, SEQ ID NO:31, SEQ ID NO:33, and SEQ ID NO:35, a nucleic acidmolecule comprising an allelic variant of a nucleic acid moleculecomprising any of said nucleic acid sequences, and a nucleic acidmolecule comprising a degenerate of a nucleic acid molecule comprisingany of said nucleic acid sequences.
 28. A nucleic acid molecule selectedfrom the group consisting of: (a) a nucleic acid molecule encoding aprotein of claim 26; (b) a nucleic acid molecule encoding a proteincomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ BNO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ IDNO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ IDNO:32, SEQ ID NO:34 and SEQ ID NO:36; (c) a nucleic acid moleculecomprising a nucleic acid sequence selected from the group consisting ofSEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ IDNO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ IDNO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ IDNO:31, SEQ ID NO:33, and SEQ ID NO:35; (d) a nucleic acid moleculecomprising an allelic variant of a nucleic acid molecule of (c); (e) anucleic acid molecule comprising a degenerate of a nucleic acid moleculeof (c); and (f) a nucleic acid molecule fully complementary to any ofsaid nucleic acid molecules of (a), (b), (c), (d) or (e).
 29. Arecombinant molecule comprising a nucleic acid molecule of claim
 28. 30.A recombinant cell comprising a nucleic acid molecule of claim
 28. 31. Amethod to produce a recombinant antigen of claim 26, said methodcomprising culturing a recombinant cell of claim 30 and recovering saidrecombinant antigen.
 32. The recombinant antigen of claim 26, whereinsaid recombinant antigen further comprises a component selected from thegroup consisting of a fusion segment and a ligand.
 33. The recombinantantigen of claim 26, wherein said recombinant antigen further comprisesa detectable marker.
 34. An assay to determine the immune status of ananimal, said assay comprising: (a) a recombinant infectious agentantigen that is specific for detecting an antibody selective for saidinfectious agent, presence of said antibody being indicative of theimmune status of said animal; and (b) a means to detect an antibody thatselectively binds to said recombinant antigen.
 35. The assay of claim34, wherein said means comprises a detection reagent.
 36. The assay ofclaim 34, wherein said assay further comprises: (a) a solid supportcomprising a test area and a reference area; and (b) a referencereagent.
 37. The assay of claim 34, wherein said test area comprisessaid recombinant antigen.
 38. The assay of claim 34, wherein said assayfurther comprises a control area for assay validation.
 39. The assay ofclaim 34, wherein said recombinant antigen comprises a recombinantprotein selected from the group consisting of PFCVCP₆₇₁, PFCVCP₅₄₇,PFPVVP2₅₈₄, PFPVVP2C₂₄₃, PFPVpVP12620, PFPVpVP2₄₇₇, PFHVgB₉₄₃,PFHVgB₂₅₀, PFHVgC₅₃₄, PFHVgC₄₆₇, PFHVgC_(467(opt)), PFHVgD₃₇₄,PFHVgD₃₀₀, PFeLVp27₂₅₃, PFeLVp27₆₁₉, PFeLVp27-gp70₆₁₁, PCDVH₆₀₄, andPCDVF₆₆₂.